Variant 14-23419456-A-T 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_000257.4(MYH7):c.3853+27T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,612,690 control chromosomes in the GnomAD database, including 107,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 14385 hom., cov: 31)

Exomes 𝑓: 0.35 ( 93422 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.406

Variant links:

Genes affected

MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

MYH7 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=-0.97).

BP6

Variant 14-23419456-A-T is Benign according to our data. Variant chr14-23419456-A-T is described in ClinVar as [Benign]. Clinvar id is 255629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23419456-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH7	NM_000257.4 linkuse as main transcript	c.3853+27T>A		intron_variant		ENST00000355349.4
MYH7	NM_001407004.1 linkuse as main transcript	c.3853+27T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH7	ENST00000355349.4 linkuse as main transcript	c.3853+27T>A		intron_variant		1	NM_000257.4	P1

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61834

AN:

151666

Hom.:

14351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.0803

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.405

GnomAD3 exomes

AF:

0.306

AC:

76783

AN:

250880

Hom.:

13846

AF XY:

0.304

AC XY:

41225

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.634

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.395

Gnomad EAS exome

AF:

0.0783

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.261

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.347

AC:

506871

AN:

1460906

Hom.:

93422

Cov.:

AF XY:

0.343

AC XY:

249329

AN XY:

726800

show subpopulations

Gnomad4 AFR exome

AF:

0.640

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.0554

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.367

Gnomad4 OTH exome

AF:

0.347

GnomAD4 genome

AF:

0.408

AC:

61902

AN:

151784

Hom.:

14385

Cov.:

AF XY:

0.395

AC XY:

29294

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.632

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.384

Gnomad4 EAS

AF:

0.0805

Gnomad4 SAS

AF:

0.214

Gnomad4 FIN

AF:

0.263

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.400

Alfa

AF:

0.302

Hom.:

1247

Bravo

AF:

0.417

Asia WGS

AF:

0.175

AC:

610

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.53

DANN

Benign

0.64

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