rs178637

chr14-23385063-T-C

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.5164-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 1,613,572 control chromosomes in the GnomAD database, including 5,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (526 hom., cov: 32)
  • Exomes 𝑓: 0.081 (5298 hom.)
• Consequence: MYH6 NM_002471.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.698

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=-0.87).
• BP6: Variant 14-23385063-T-C is Benign according to our data. Variant chr14-23385063-T-C is described in ClinVar as [Benign]. Clinvar id is 258713.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23385063-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH6	NM_002471.4	c.5164-22A>G		intron_variant		ENST00000405093.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH6	ENST00000405093.9	c.5164-22A>G		intron_variant		5	NM_002471.4	P1

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11836 AN: 152016 Hom.: 528 Cov.: 32

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0557

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.0637

Gnomad SAS AF: 0.0778

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0742

GnomAD3 exomes AF: 0.0793 AC: 19936 AN: 251448 Hom.: 934 AF XY: 0.0805 AC XY: 10940 AN XY: 135912

Gnomad AFR exome AF: 0.0636

Gnomad AMR exome AF: 0.0296

Gnomad ASJ exome AF: 0.0702

Gnomad EAS exome AF: 0.0624

Gnomad SAS exome AF: 0.0806

Gnomad FIN exome AF: 0.167

Gnomad NFE exome AF: 0.0831

Gnomad OTH exome AF: 0.0776

GnomAD4 exome AF: 0.0811 AC: 118582 AN: 1461438 Hom.: 5298 Cov.: 34 AF XY: 0.0815 AC XY: 59254 AN XY: 727072

Gnomad4 AFR exome AF: 0.0609

Gnomad4 AMR exome AF: 0.0321

Gnomad4 ASJ exome AF: 0.0698

Gnomad4 EAS exome AF: 0.0850

Gnomad4 SAS exome AF: 0.0797

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.0805

Gnomad4 OTH exome AF: 0.0787

GnomAD4 genome AF: 0.0777 AC: 11824 AN: 152134 Hom.: 526 Cov.: 32 AF XY: 0.0810 AC XY: 6022 AN XY: 74368

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.0555

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.0638

Gnomad4 SAS AF: 0.0771

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.0811

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.0769 Hom.: 263

Bravo AF: 0.0683

Asia WGS AF: 0.0760 AC: 264 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	-0.87
Cadd	Benign	1.2
Dann	Benign	0.58

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: rs178637; hg19: chr14-23854272; COSMIC: COSV62453249; COSMIC: COSV62453249;