rs12147570

Positions:

• chr14-23412711-G-T

Variant summary

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

The 14-23412711-G-T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 977,046 control chromosomes in the GnomAD database, including 10,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1362 hom., cov: 32)
  • Exomes 𝑓: 0.14 (8734 hom.)
• Consequence: MYH7 ENST00000355349.4 downstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.364

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=-0.7).
• BP6: Variant 14-23412711-G-T is Benign according to our data. Variant chr14-23412711-G-T is described in ClinVar as [Benign]. Clinvar id is 1252265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23412711-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH7	NM_000257.4			downstream_gene_variant		ENST00000355349.4	NP_000248.2
MYH7	NM_001407004.1			downstream_gene_variant			NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4			downstream_gene_variant		1	NM_000257.4	ENSP00000347507	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19377 AN: 152078 Hom.: 1360 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.136 AC: 112067 AN: 824850 Hom.: 8734 Cov.: 11 AF XY: 0.132 AC XY: 56659 AN XY: 427936

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.0640

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.0000588

Gnomad4 SAS exome AF: 0.0474

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.127 AC: 19395 AN: 152196 Hom.: 1362 Cov.: 32 AF XY: 0.124 AC XY: 9208 AN XY: 74424

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0910

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0404

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.131

Alfa AF: 0.144 Hom.: 2256

Bravo AF: 0.125

Asia WGS AF: 0.0290 AC: 103 AN: 3478

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	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	-0.70
CADD	Benign	11
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12147570; hg19: chr14-23881920;