CNOT4 : c.1642G>A

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.1642G>A	p.V548I (Val > Ile)	substitution	missense	chr7:135048804 (reverse strand)	0.26531083

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.26531083 (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
ExAC	0.24690594 15162 / 61408	0.18907975 1541 / 8150	0.51571637 4233 / 8208	0.17576433 2840 / 16158	0.37852361 4297 / 11352	0.24612580 1620 / 6582	0.24642857 207 / 840	0.26531083 29900 / 112698
ESP	0.25013 996 / 3982	0.20091 352 / 1752						0.23509 1348 / 5734
1KG	0.24257 196 / 808	0.15809 209 / 1322	0.52183 526 / 1008	0.17178 168 / 978	0.31988 222 / 694	0.25758 51 / 198		0.27396 1372 / 5008

View sub-population details for 1000 Genomes (1KG) data

Hide sub-population details for 1000 Genomes (1KG) data

0.29121 53 / 182 British	0.16393 20 / 122 African-American	0.51613 96 / 186 Chinese Dai	0.19186 33 / 172 Bengali	0.32447 61 / 188 Colombian
0.17757 38 / 214 Iberian	0.17708 34 / 192 African-Caribbean	0.56311 116 / 206 Han, Beijing	0.16990 35 / 206 Gujarati Indian	0.35156 45 / 128 Mexican, LA
0.23364 50 / 214 Toscani	0.18687 37 / 198 Esan, Nigeria	0.45673 95 / 208 Japanese	0.17157 35 / 204 Indian Telugu	0.39412 67 / 170 Peruvian
0.27778 55 / 198 Utah Europeans	0.08407 19 / 226 Gambian	0.51515 102 / 198 Kinh, Vietnam	0.16146 31 / 192 Punjabi, Lahore	0.23558 49 / 208 Puerto Rican
	0.17172 34 / 198 Luhya, Kenya	0.55714 117 / 210 Southern Han	0.16667 34 / 204 Tamil
	0.08824 15 / 170 Mende
	0.23148 50 / 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	ENST00000541284		NM_001190850.1
Protein	ENSP00000445508			F8VQP3

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 12.5% of algorithms have predicted that this variant will adversely affect protein function
tolerated	conservative	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
deleterious	polymorphism (auto)	neutral	tolerated

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.