Variant rs3729810 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.999+44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0961 in 1,508,828 control chromosomes in the GnomAD database, including 11,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 4003 hom., cov: 32)

Exomes 𝑓: 0.087 ( 7446 hom. )

Consequence

MYH7
NM_000257.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.265

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=-0.82).

BP6

Variant 14-23430516-A-G is Benign according to our data. Variant chr14-23430516-A-G is described in ClinVar as [Benign]. Clinvar id is 255636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23430516-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 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.999+44T>C		intron_variant		ENST00000355349.4	NP_000248.2	P12883
MYH7	NM_001407004.1 linkuse as main transcript	c.999+44T>C		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.999+44T>C		intron_variant		1	NM_000257.4	ENSP00000347507.3		P12883

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26175

AN:

151774

Hom.:

3989

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.0948

Gnomad ASJ

AF:

0.0972

Gnomad EAS

AF:

0.0161

Gnomad SAS

AF:

0.0798

Gnomad FIN

AF:

0.0566

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0834

Gnomad OTH

AF:

0.156

GnomAD3 exomes

AF:

0.0951

AC:

22185

AN:

233304

Hom.:

1991

AF XY:

0.0908

AC XY:

11406

AN XY:

125626

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.0618

Gnomad ASJ exome

AF:

0.0986

Gnomad EAS exome

AF:

0.0141

Gnomad SAS exome

AF:

0.0801

Gnomad FIN exome

AF:

0.0549

Gnomad NFE exome

AF:

0.0840

Gnomad OTH exome

AF:

0.0941

GnomAD4 exome

AF:

0.0875

AC:

118718

AN:

1356936

Hom.:

7446

Cov.:

AF XY:

0.0866

AC XY:

58831

AN XY:

679258

show subpopulations

Gnomad4 AFR exome

AF:

0.430

Gnomad4 AMR exome

AF:

0.0664

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.0120

Gnomad4 SAS exome

AF:

0.0796

Gnomad4 FIN exome

AF:

0.0563

Gnomad4 NFE exome

AF:

0.0814

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.173

AC:

26233

AN:

151892

Hom.:

4003

Cov.:

AF XY:

0.166

AC XY:

12290

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.418

Gnomad4 AMR

AF:

0.0946

Gnomad4 ASJ

AF:

0.0972

Gnomad4 EAS

AF:

0.0159

Gnomad4 SAS

AF:

0.0799

Gnomad4 FIN

AF:

0.0566

Gnomad4 NFE

AF:

0.0834

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.131

Hom.:

488

Bravo

AF:

0.186

Asia WGS

AF:

0.0890

AC:

307

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.1

DANN

Benign

0.74

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