14-23425874-T-C

Position:

• chr14-23425874-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.2163-56A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,610,288 control chromosomes in the GnomAD database, including 29,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6968 hom., cov: 32)
  • Exomes 𝑓: 0.16 (22083 hom.)
• Consequence: MYH7 NM_000257.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.36

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=-0.79).
• BP6: Variant 14-23425874-T-C is Benign according to our data. Variant chr14-23425874-T-C is described in ClinVar as [Benign]. Clinvar id is 1265302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23425874-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH7	NM_000257.4	c.2163-56A>G		intron_variant		ENST00000355349.4	NP_000248.2
MYH7	NM_001407004.1	c.2163-56A>G		intron_variant			NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4	c.2163-56A>G		intron_variant		1	NM_000257.4	ENSP00000347507.3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38815 AN: 151990 Hom.: 6955 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0808

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.162 AC: 235501 AN: 1458180 Hom.: 22083 Cov.: 34 AF XY: 0.162 AC XY: 117196 AN XY: 725360

Gnomad4 AFR exome AF: 0.527

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.0561

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.155

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.255 AC: 38859 AN: 152108 Hom.: 6968 Cov.: 32 AF XY: 0.248 AC XY: 18440 AN XY: 74350

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0810

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.232

Alfa AF: 0.212 Hom.: 578

Bravo AF: 0.267

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
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	-0.79
CADD	Benign	5.2
DANN	Benign	0.81

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: rs3729818; hg19: chr14-23895083; COSMIC: COSV62520021;