Variant 14-23413975-C-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.5655+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,613,918 control chromosomes in the GnomAD database, including 21,580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3257 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18323 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.39

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-23413975-C-T is Benign according to our data. Variant chr14-23413975-C-T is described in ClinVar as [Benign]. Clinvar id is 255632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23413975-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 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.5655+32G>A		intron_variant		ENST00000355349.4
MYH7	NM_001407004.1 linkuse as main transcript	c.5655+32G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH7	ENST00000355349.4 linkuse as main transcript	c.5655+32G>A		intron_variant		1	NM_000257.4	P1

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28201

AN:

152058

Hom.:

3249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0420

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.125

AC:

31461

AN:

251330

Hom.:

2709

AF XY:

0.120

AC XY:

16342

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.0688

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0440

Gnomad FIN exome

AF:

0.105

Gnomad NFE exome

AF:

0.156

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.150

AC:

218811

AN:

1461740

Hom.:

18323

Cov.:

AF XY:

0.146

AC XY:

106290

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.318

Gnomad4 AMR exome

AF:

0.0748

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0471

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.162

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.186

AC:

28236

AN:

152178

Hom.:

3257

Cov.:

AF XY:

0.179

AC XY:

13291

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0416

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.178

Alfa

AF:

0.156

Hom.:

2076

Bravo

AF:

0.191

Asia WGS

AF:

0.0410

AC:

145

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.9

DANN

Benign

0.57

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