NM_000257.4:c.4353+42G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000257.4(MYH7):c.4353+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 1,612,164 control chromosomes in the GnomAD database, including 1,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 871 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 761 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.19

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:

MHRT (HGNC:51291): (myosin heavy chain associated RNA transcript) This gene encodes a spliced long non-coding RNA that may act as a cardioprotective agent in the heart. Based on a study of a similar gene in mouse, the encoded transcript may regulate chromatin remodeling by acting as a decoy to the BRG1 chromatin repressor complex thus preventing it from binding to its genomic targets. Blocking the actions of BRG1 could be crucial in protecting the heart from pathological hypertrophy. [provided by RefSeq, Dec 2014]

MHRT 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=-0.88).

BP6

Variant 14-23417461-C-T is Benign according to our data. Variant chr14-23417461-C-T is described in ClinVar as [Benign]. Clinvar id is 188635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23417461-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH7	NM_000257.4 link	c.4353+42G>A	intron_variant	Intron 31 of 39	ENST00000355349.4	NP_000248.2	P12883
MYH7	NM_001407004.1 link	c.4353+42G>A	intron_variant	Intron 30 of 38		NP_001393933.1
MHRT	NR_126491.1 link	n.814-72C>T	intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4 link	c.4353+42G>A		intron_variant	Intron 31 of 39	1	NM_000257.4	ENSP00000347507.3		P12883

Frequencies

GnomAD3 genomes

AF:

0.0588

AC:

8943

AN:

152144

Hom.:

869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0238

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.0487

GnomAD3 exomes

AF:

0.0156

AC:

3919

AN:

250634

Hom.:

372

AF XY:

0.0114

AC XY:

1543

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.000896

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000681

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.00595

AC:

8693

AN:

1459902

Hom.:

761

Cov.:

AF XY:

0.00510

AC XY:

3703

AN XY:

726256

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.0121

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000420

Gnomad4 OTH exome

AF:

0.0134

GnomAD4 genome

AF:

0.0589

AC:

8961

AN:

152262

Hom.:

871

Cov.:

AF XY:

0.0556

AC XY:

4141

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.0237

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.0482

Alfa

AF:

0.0258

Hom.:

Bravo

AF:

0.0667

Asia WGS

AF:

0.0120

AC:

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

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.62

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