HFE : c.187C>G

HFE gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.187C>Gp.H63D (His > Asp)substitutionmissense chr6:26091179 (forward strand)0.10659924

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.10659924 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

Detection in Population Databases



Database European African East Asian South Asian American Finnish Other Total
ExAC0.13677365
9128 / 66738		0.02902172
302 / 10406		0.03651491
316 / 8654		0.07788275
1286 / 16512		0.09588804
1110 / 11576		0.10311461
682 / 6614		0.12995595
118 / 908		0.10659924
12942 / 121408
ESP 0.15128
1301 / 8600		 0.03155
139 / 4406		 0.11072
1440 / 13006
1KG
 0.18688
151 / 808		 0.01135
15 / 1322		 0.02877
29 / 1008		 0.07055
69 / 978		 0.11527
80 / 694		 0.11111
22 / 198		 0.07308
366 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.18132
33 / 182
British
0.04918
6 / 122
African-American
0.02151
4 / 186
Chinese Dai
0.02907
5 / 172
Bengali
0.14894
28 / 188
Colombian
0.25234
54 / 214
Iberian
0.02083
4 / 192
African-Caribbean
0.02913
6 / 206
Han, Beijing
0.08252
17 / 206
Gujarati Indian
0.11719
15 / 128
Mexican, LA
0.17757
38 / 214
Toscani
0.00505
1 / 198
Esan, Nigeria
0.01923
4 / 208
Japanese
0.09804
20 / 204
Indian Telugu
0.06471
11 / 170
Peruvian
0.13131
26 / 198
Utah Europeans
0.00442
1 / 226
Gambian
0.04545
9 / 198
Kinh, Vietnam
0.05729
11 / 192
Punjabi, Lahore
0.12500
26 / 208
Puerto Rican
0.01010
2 / 198
Luhya, Kenya
0.02857
6 / 210
Southern Han
0.07843
16 / 204
Tamil
0.00000
0 / 170
Mende
0.00463
1 / 216
Yoruba, Nigeria

The Exome Aggregation Consortium (ExAC) is a database of 60,706 unrelated individuals sequenced as part of various disease-specific and population genetic studies. There is partial overlap between ExAC and 1000 Genomes (1KG) (1,851 of the 2,504 samples in 1KG) and the Exome Sequencing Project (ESP) (3,936 of the 6,500 samples in ESP).


Other Variant & Gene Details

Canonical Sequences
Transcript ENST00000357618 NM_000410.3
Protein ENSP00000417404 Q30201

Missense Variant Predictions
SIFT Grantham Polyphen-DIV Polyphen-VAR Summary
25% of algorithms have predicted that this variant will adversely affect protein function
damaging moderately conservative benign benign
LRT MutationTaster MutationAssessor FATHMM
neutral polymorphism (auto) low impact damaging


References

1. Roddy Walsh, Kate L. Thomson, James S. Ware, Birgit H. Funke, Jessica Woodley, Karen J. McGuire, Francesco Mazzarotto, Edward Blair, Anneke Seller, Jenny C. Taylor, Eric V. Minikel, Exome Aggregation Consortium, Daniel G. MacArthur, Martin Farrall, Stuart A. Cook and Hugh Watkins. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2016 doi:10.1038/gim.2016.90.

2. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.

3. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015 Nov;17(11):880-8.