rs17091278

Positions:

chr14-23383288-T-C

Variant summary

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

The NM_002471.4(MYH6):c.5598A>G(p.Leu1866=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,395,506 control chromosomes in the GnomAD database, including 2,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 1216 hom., cov: 29)

Exomes 𝑓: 0.014 ( 1115 hom. )

Consequence

MYH6
NM_002471.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.30

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=-0.54).

BP6

Variant 14-23383288-T-C is Benign according to our data. Variant chr14-23383288-T-C is described in ClinVar as [Benign]. Clinvar id is 258715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23383288-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 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.5598A>G	p.Leu1866=	synonymous_variant	37/39	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.5598A>G	p.Leu1866=	synonymous_variant	37/39	5	NM_002471.4	ENSP00000386041	P1
MYH6	ENST00000651452.1 linkuse as main transcript	n.825A>G		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes

AF:

0.0833

AC:

10576

AN:

126896

Hom.:

1205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0439

Gnomad ASJ

AF:

0.00182

Gnomad EAS

AF:

0.0216

Gnomad SAS

AF:

0.00950

Gnomad FIN

AF:

0.000182

Gnomad MID

AF:

0.0256

Gnomad NFE

AF:

0.00555

Gnomad OTH

AF:

0.0580

GnomAD3 exomes

AF:

0.0227

AC:

5698

AN:

251254

Hom.:

524

AF XY:

0.0179

AC XY:

2432

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.249

Gnomad AMR exome

AF:

0.0158

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.0169

Gnomad SAS exome

AF:

0.00683

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00409

Gnomad OTH exome

AF:

0.0144

GnomAD4 exome

AF:

0.0135

AC:

17136

AN:

1268540

Hom.:

1115

Cov.:

AF XY:

0.0122

AC XY:

7687

AN XY:

628584

show subpopulations

Gnomad4 AFR exome

AF:

0.275

Gnomad4 AMR exome

AF:

0.0209

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.0235

Gnomad4 SAS exome

AF:

0.00686

Gnomad4 FIN exome

AF:

0.000426

Gnomad4 NFE exome

AF:

0.00560

Gnomad4 OTH exome

AF:

0.0274

GnomAD4 genome

AF:

0.0836

AC:

10614

AN:

126966

Hom.:

1216

Cov.:

AF XY:

0.0861

AC XY:

5050

AN XY:

58668

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.0437

Gnomad4 ASJ

AF:

0.00182

Gnomad4 EAS

AF:

0.0216

Gnomad4 SAS

AF:

0.00926

Gnomad4 FIN

AF:

0.000182

Gnomad4 NFE

AF:

0.00555

Gnomad4 OTH

AF:

0.0577

Alfa

AF:

0.0368

Hom.:

231

Bravo

AF:

0.0829

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.00496

EpiControl

AF:

0.00445

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

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	GeneDx	Sep 29, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	Jun 16, 2016	- -

Hypertrophic cardiomyopathy 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 25, 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

-0.54

CADD

Benign

4.6

DANN

Benign

0.76

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