Variant rs178642 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002471.4(MYH6):c.4526-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 1,613,696 control chromosomes in the GnomAD database, including 194,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17614 hom., cov: 31)

Exomes 𝑓: 0.49 ( 177164 hom. )

Consequence

MYH6
NM_002471.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.242

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 14-23387687-A-G is Benign according to our data. Variant chr14-23387687-A-G is described in ClinVar as [Benign]. Clinvar id is 258710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23387687-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 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.4526-34T>C		intron_variant		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.4526-34T>C		intron_variant		5	NM_002471.4	ENSP00000386041.3		P13533

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72653

AN:

151720

Hom.:

17595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.367

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.490

Gnomad OTH

AF:

0.450

GnomAD3 exomes

AF:

0.500

AC:

125823

AN:

251412

Hom.:

32163

AF XY:

0.492

AC XY:

66850

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.413

Gnomad AMR exome

AF:

0.553

Gnomad ASJ exome

AF:

0.536

Gnomad EAS exome

AF:

0.621

Gnomad SAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.575

Gnomad NFE exome

AF:

0.490

Gnomad OTH exome

AF:

0.497

GnomAD4 exome

AF:

0.489

AC:

715226

AN:

1461858

Hom.:

177164

Cov.:

AF XY:

0.487

AC XY:

353879

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.414

Gnomad4 AMR exome

AF:

0.553

Gnomad4 ASJ exome

AF:

0.531

Gnomad4 EAS exome

AF:

0.647

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.566

Gnomad4 NFE exome

AF:

0.486

Gnomad4 OTH exome

AF:

0.491

GnomAD4 genome

AF:

0.479

AC:

72707

AN:

151838

Hom.:

17614

Cov.:

AF XY:

0.485

AC XY:

35957

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.516

Gnomad4 EAS

AF:

0.630

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.583

Gnomad4 NFE

AF:

0.490

Gnomad4 OTH

AF:

0.444

Alfa

AF:

0.486

Hom.:

18742

Bravo

AF:

0.474

Asia WGS

AF:

0.461

AC:

1600

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.9

DANN

Benign

0.83

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