Variant rs412768 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.1962+39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,605,766 control chromosomes in the GnomAD database, including 80,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9778 hom., cov: 33)

Exomes 𝑓: 0.31 ( 70493 hom. )

Consequence

MYH6
NM_002471.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.77

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=-0.9).

BP6

Variant 14-23397504-A-G is Benign according to our data. Variant chr14-23397504-A-G is described in ClinVar as [Benign]. Clinvar id is 258707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23397504-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 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.1962+39T>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.1962+39T>C		intron_variant		5	NM_002471.4	ENSP00000386041	P1

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52791

AN:

152070

Hom.:

9742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.475

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.260

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.350

GnomAD3 exomes

AF:

0.289

AC:

72491

AN:

251200

Hom.:

11253

AF XY:

0.289

AC XY:

39279

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.474

Gnomad AMR exome

AF:

0.191

Gnomad ASJ exome

AF:

0.398

Gnomad EAS exome

AF:

0.165

Gnomad SAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.308

GnomAD4 exome

AF:

0.306

AC:

445140

AN:

1453578

Hom.:

70493

Cov.:

AF XY:

0.305

AC XY:

220879

AN XY:

723650

show subpopulations

Gnomad4 AFR exome

AF:

0.489

Gnomad4 AMR exome

AF:

0.199

Gnomad4 ASJ exome

AF:

0.407

Gnomad4 EAS exome

AF:

0.148

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.261

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.319

GnomAD4 genome

AF:

0.347

AC:

52866

AN:

152188

Hom.:

9778

Cov.:

AF XY:

0.343

AC XY:

25507

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.475

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.409

Gnomad4 EAS

AF:

0.163

Gnomad4 SAS

AF:

0.272

Gnomad4 FIN

AF:

0.260

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.355

Alfa

AF:

0.329

Hom.:

4364

Bravo

AF:

0.352

Asia WGS

AF:

0.247

AC:

861

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

-0.90

CADD

Benign

0.036

DANN

Benign

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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