rs7159367

chr14-23418436-T-C

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.547

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 14-23418436-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	UniProt
MYH7	NM_000257.4	c.3973-30A>G		intron_variant		ENST00000355349.4
MYH7	NM_001407004.1	c.3973-30A>G		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64316 AN: 151950 Hom.: 15843 Cov.: 33

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

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.: 36 AF XY: 0.346 AC XY: 244770 AN XY: 708410

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.: 33 AF XY: 0.410 AC XY: 30494 AN XY: 74326

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:4

Revision: criteria provided, multiple submitters, no conflicts

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

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	13
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

Other links and lift over

dbSNP: rs7159367; hg19: chr14-23887645;