Variant rs451794 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002471.4(MYH6):c.4011G>A(p.Ser1337Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,599,760 control chromosomes in the GnomAD database, including 9,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 564 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9184 hom. )

Consequence

MYH6
NM_002471.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -9.97

Variant links:

Genes affected

MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]

MYH6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 14-23389023-C-T is Benign according to our data. Variant chr14-23389023-C-T is described in ClinVar as [Benign]. Clinvar id is 44501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23389023-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-9.98 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH6	NM_002471.4 linkuse as main transcript	c.4011G>A	p.Ser1337Ser	synonymous_variant	29/39	ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9 linkuse as main transcript	c.4011G>A	p.Ser1337Ser	synonymous_variant	29/39	5	NM_002471.4	ENSP00000386041.3		P13533

Frequencies

GnomAD3 genomes

AF:

0.0767

AC:

11538

AN:

150486

Hom.:

562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.0914

Gnomad AMR

AF:

0.0596

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.000400

Gnomad SAS

AF:

0.0338

Gnomad FIN

AF:

0.0856

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.0763

GnomAD3 exomes

AF:

0.0770

AC:

19173

AN:

248882

Hom.:

983

AF XY:

0.0777

AC XY:

10469

AN XY:

134788

show subpopulations

Gnomad AFR exome

AF:

0.0223

Gnomad AMR exome

AF:

0.0403

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.000382

Gnomad SAS exome

AF:

0.0390

Gnomad FIN exome

AF:

0.0817

Gnomad NFE exome

AF:

0.111

Gnomad OTH exome

AF:

0.0913

GnomAD4 exome

AF:

0.106

AC:

153783

AN:

1449152

Hom.:

9184

Cov.:

AF XY:

0.104

AC XY:

75133

AN XY:

720476

show subpopulations

Gnomad4 AFR exome

AF:

0.0191

Gnomad4 AMR exome

AF:

0.0425

Gnomad4 ASJ exome

AF:

0.147

Gnomad4 EAS exome

AF:

0.000208

Gnomad4 SAS exome

AF:

0.0399

Gnomad4 FIN exome

AF:

0.0833

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.100

GnomAD4 genome

AF:

0.0766

AC:

11544

AN:

150608

Hom.:

564

Cov.:

AF XY:

0.0752

AC XY:

5527

AN XY:

73490

show subpopulations

Gnomad4 AFR

AF:

0.0231

Gnomad4 AMR

AF:

0.0596

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.000401

Gnomad4 SAS

AF:

0.0338

Gnomad4 FIN

AF:

0.0856

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.0755

Alfa

AF:

0.100

Hom.:

363

Bravo

AF:

0.0726

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.112

EpiControl

AF:

0.112

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 27, 2011	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	May 13, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypertrophic cardiomyopathy 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 15, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.44

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over