Variant rs178637 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.5164-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 1,613,572 control chromosomes in the GnomAD database, including 5,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.078 ( 526 hom., cov: 32)

Exomes 𝑓: 0.081 ( 5298 hom. )

Consequence

MYH6
NM_002471.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.698

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 14-23385063-T-C is Benign according to our data. Variant chr14-23385063-T-C is described in ClinVar as [Benign]. Clinvar id is 258713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23385063-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH6	NM_002471.4 link	c.5164-22A>G		intron_variant	Intron 34 of 38	ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9 link	c.5164-22A>G		intron_variant	Intron 34 of 38	5	NM_002471.4	ENSP00000386041.3		P13533

Frequencies

GnomAD3 genomes

AF:

0.0779

AC:

11836

AN:

152016

Hom.:

528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0615

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0557

Gnomad ASJ

AF:

0.0729

Gnomad EAS

AF:

0.0637

Gnomad SAS

AF:

0.0778

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0811

Gnomad OTH

AF:

0.0742

GnomAD3 exomes

AF:

0.0793

AC:

19936

AN:

251448

Hom.:

934

AF XY:

0.0805

AC XY:

10940

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.0636

Gnomad AMR exome

AF:

0.0296

Gnomad ASJ exome

AF:

0.0702

Gnomad EAS exome

AF:

0.0624

Gnomad SAS exome

AF:

0.0806

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.0831

Gnomad OTH exome

AF:

0.0776

GnomAD4 exome

AF:

0.0811

AC:

118582

AN:

1461438

Hom.:

5298

Cov.:

AF XY:

0.0815

AC XY:

59254

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.0609

Gnomad4 AMR exome

AF:

0.0321

Gnomad4 ASJ exome

AF:

0.0698

Gnomad4 EAS exome

AF:

0.0850

Gnomad4 SAS exome

AF:

0.0797

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.0805

Gnomad4 OTH exome

AF:

0.0787

GnomAD4 genome

AF:

0.0777

AC:

11824

AN:

152134

Hom.:

526

Cov.:

AF XY:

0.0810

AC XY:

6022

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0612

Gnomad4 AMR

AF:

0.0555

Gnomad4 ASJ

AF:

0.0729

Gnomad4 EAS

AF:

0.0638

Gnomad4 SAS

AF:

0.0771

Gnomad4 FIN

AF:

0.168

Gnomad4 NFE

AF:

0.0811

Gnomad4 OTH

AF:

0.0729

Alfa

AF:

0.0769

Hom.:

263

Bravo

AF:

0.0683

Asia WGS

AF:

0.0760

AC:

264

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

-0.87

CADD

Benign

1.2

DANN

Benign

0.58

BranchPoint Hunter

1.0

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