rs178642

chr14-23387687-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002471.4(MYH6):c.4526-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 1,613,696 control chromosomes in the GnomAD database, including 194,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (17614 hom., cov: 31)
  • Exomes 𝑓: 0.49 (177164 hom.)
• Consequence: MYH6 NM_002471.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.242

Genes affected

MYH6 (HGNC:7576): (myosin heavy chain 6) Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 14-23387687-A-G is Benign according to our data. Variant chr14-23387687-A-G is described in ClinVar as [Benign]. Clinvar id is 258710.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23387687-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH6	NM_002471.4	c.4526-34T>C		intron_variant		ENST00000405093.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH6	ENST00000405093.9	c.4526-34T>C		intron_variant		5	NM_002471.4	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72653 AN: 151720 Hom.: 17595 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.450

GnomAD3 exomes AF: 0.500 AC: 125823 AN: 251412 Hom.: 32163 AF XY: 0.492 AC XY: 66850 AN XY: 135872

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.553

Gnomad ASJ exome AF: 0.536

Gnomad EAS exome AF: 0.621

Gnomad SAS exome AF: 0.390

Gnomad FIN exome AF: 0.575

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.489 AC: 715226 AN: 1461858 Hom.: 177164 Cov.: 70 AF XY: 0.487 AC XY: 353879 AN XY: 727228

Gnomad4 AFR exome AF: 0.414

Gnomad4 AMR exome AF: 0.553

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.566

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.479 AC: 72707 AN: 151838 Hom.: 17614 Cov.: 31 AF XY: 0.485 AC XY: 35957 AN XY: 74182

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.444

Alfa AF: 0.486 Hom.: 18742

Bravo AF: 0.474

Asia WGS AF: 0.461 AC: 1600 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	1.9
Dann	Benign	0.83

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: rs178642; hg19: chr14-23856896; COSMIC: COSV62448750; COSMIC: COSV62448750;