Variant 14-23418436-T-C 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.3973-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,582,748 control chromosomes in the GnomAD database, including 109,201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 15879 hom., cov: 33)

Exomes 𝑓: 0.35 ( 93322 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.547

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 14-23418436-T-C is Benign according to our data. Variant chr14-23418436-T-C is described in ClinVar as [Benign]. Clinvar id is 255630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23418436-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH7	NM_000257.4 linkuse as main transcript	c.3973-30A>G		intron_variant		ENST00000355349.4	NP_000248.2
MYH7	NM_001407004.1 linkuse as main transcript	c.3973-30A>G		intron_variant			NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4 linkuse as main transcript	c.3973-30A>G		intron_variant		1	NM_000257.4	ENSP00000347507	P1

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64316

AN:

151950

Hom.:

15843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.683

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.0807

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.312

AC:

70251

AN:

225032

Hom.:

12965

AF XY:

0.310

AC XY:

37811

AN XY:

121814

show subpopulations

Gnomad AFR exome

AF:

0.688

Gnomad AMR exome

AF:

0.184

Gnomad ASJ exome

AF:

0.412

Gnomad EAS exome

AF:

0.0787

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.329

GnomAD4 exome

AF:

0.350

AC:

500121

AN:

1430680

Hom.:

93322

Cov.:

AF XY:

0.346

AC XY:

244770

AN XY:

708410

show subpopulations

Gnomad4 AFR exome

AF:

0.692

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.411

Gnomad4 EAS exome

AF:

0.0555

Gnomad4 SAS exome

AF:

0.224

Gnomad4 FIN exome

AF:

0.273

Gnomad4 NFE exome

AF:

0.367

Gnomad4 OTH exome

AF:

0.352

GnomAD4 genome

AF:

0.423

AC:

64390

AN:

152068

Hom.:

15879

Cov.:

AF XY:

0.410

AC XY:

30494

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.683

Gnomad4 AMR

AF:

0.289

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.0809

Gnomad4 SAS

AF:

0.214

Gnomad4 FIN

AF:

0.263

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.411

Alfa

AF:

0.393

Hom.:

2369

Bravo

AF:

0.435

Asia WGS

AF:

0.179

AC:

625

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.70

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