Variant rs2284651 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.5791-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,562,884 control chromosomes in the GnomAD database, including 115,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16634 hom., cov: 32)

Exomes 𝑓: 0.36 ( 98491 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.89

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=-0.94).

BP6

Variant 14-23412935-T-C is Benign according to our data. Variant chr14-23412935-T-C is described in ClinVar as [Benign]. Clinvar id is 1263654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23412935-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 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.5791-64A>G		intron_variant		ENST00000355349.4	NP_000248.2
MYH7	NM_001407004.1 linkuse as main transcript	c.5791-64A>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.5791-64A>G		intron_variant		1	NM_000257.4	ENSP00000347507	P1

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66576

AN:

151902

Hom.:

16591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.687

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.449

GnomAD4 exome

AF:

0.364

AC:

514117

AN:

1410864

Hom.:

98491

AF XY:

0.361

AC XY:

254578

AN XY:

704664

show subpopulations

Gnomad4 AFR exome

AF:

0.696

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.438

Gnomad4 EAS exome

AF:

0.136

Gnomad4 SAS exome

AF:

0.271

Gnomad4 FIN exome

AF:

0.280

Gnomad4 NFE exome

AF:

0.377

Gnomad4 OTH exome

AF:

0.372

GnomAD4 genome

AF:

0.439

AC:

66666

AN:

152020

Hom.:

16634

Cov.:

AF XY:

0.426

AC XY:

31666

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.687

Gnomad4 AMR

AF:

0.316

Gnomad4 ASJ

AF:

0.426

Gnomad4 EAS

AF:

0.154

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.375

Gnomad4 OTH

AF:

0.452

Alfa

AF:

0.347

Hom.:

2094

Bravo

AF:

0.452

Asia WGS

AF:

0.272

AC:

947

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.075

DANN

Benign

0.53

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