Variant rs8006357 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.5565+22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,607,124 control chromosomes in the GnomAD database, including 55,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4298 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50834 hom. )

Consequence

MYH6
NM_002471.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.558

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=-0.89).

BP6

Variant 14-23384420-T-C is Benign according to our data. Variant chr14-23384420-T-C is described in ClinVar as [Benign]. Clinvar id is 258714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23384420-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH6	NM_002471.4 linkuse as main transcript	c.5565+22A>G		intron_variant		ENST00000405093.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH6	ENST00000405093.9 linkuse as main transcript	c.5565+22A>G		intron_variant		5	NM_002471.4	P1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35190

AN:

152028

Hom.:

4291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.357

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.272

GnomAD3 exomes

AF:

0.250

AC:

61649

AN:

246722

Hom.:

8378

AF XY:

0.262

AC XY:

35010

AN XY:

133838

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.326

Gnomad EAS exome

AF:

0.189

Gnomad SAS exome

AF:

0.359

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.264

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.260

AC:

378545

AN:

1454978

Hom.:

50834

Cov.:

AF XY:

0.264

AC XY:

191093

AN XY:

724158

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.181

Gnomad4 ASJ exome

AF:

0.327

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.358

Gnomad4 FIN exome

AF:

0.215

Gnomad4 NFE exome

AF:

0.261

Gnomad4 OTH exome

AF:

0.253

GnomAD4 genome

AF:

0.232

AC:

35223

AN:

152146

Hom.:

4298

Cov.:

AF XY:

0.231

AC XY:

17219

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.167

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.342

Gnomad4 EAS

AF:

0.190

Gnomad4 SAS

AF:

0.360

Gnomad4 FIN

AF:

0.217

Gnomad4 NFE

AF:

0.256

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.262

Hom.:

11053

Bravo

AF:

0.228

Asia WGS

AF:

0.264

AC:

921

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

-0.89

CADD

Benign

1.4

DANN

Benign

0.51

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