rs3729833

chr14-23413975-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.39

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]

ACMG classification

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	c.5655+32G>A		intron_variant		ENST00000355349.4
MYH7	NM_001407004.1	c.5655+32G>A		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28201 AN: 152058 Hom.: 3249 Cov.: 32

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

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.: 34 AF XY: 0.146 AC XY: 106290 AN XY: 727178

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.: 32 AF XY: 0.179 AC XY: 13291 AN XY: 74408

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

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	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

Other links and lift over

dbSNP: rs3729833; hg19: chr14-23883184;