rs412768

chr14-23397504-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.1962+39T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,605,766 control chromosomes in the GnomAD database, including 80,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9778 hom., cov: 33)
  • Exomes 𝑓: 0.31 (70493 hom.)
• Consequence: MYH6 NM_002471.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.77

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=-0.9).
• BP6: Variant 14-23397504-A-G is Benign according to our data. Variant chr14-23397504-A-G is described in ClinVar as [Benign]. Clinvar id is 258707.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23397504-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH6	NM_002471.4	c.1962+39T>C		intron_variant		ENST00000405093.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH6	ENST00000405093.9	c.1962+39T>C		intron_variant		5	NM_002471.4	P1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52791 AN: 152070 Hom.: 9742 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.350

GnomAD3 exomes AF: 0.289 AC: 72491 AN: 251200 Hom.: 11253 AF XY: 0.289 AC XY: 39279 AN XY: 135796

Gnomad AFR exome AF: 0.474

Gnomad AMR exome AF: 0.191

Gnomad ASJ exome AF: 0.398

Gnomad EAS exome AF: 0.165

Gnomad SAS exome AF: 0.276

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.308

GnomAD4 exome AF: 0.306 AC: 445140 AN: 1453578 Hom.: 70493 Cov.: 30 AF XY: 0.305 AC XY: 220879 AN XY: 723650

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.312

Gnomad4 OTH exome AF: 0.319

GnomAD4 genome AF: 0.347 AC: 52866 AN: 152188 Hom.: 9778 Cov.: 33 AF XY: 0.343 AC XY: 25507 AN XY: 74396

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.355

Alfa AF: 0.329 Hom.: 4364

Bravo AF: 0.352

Asia WGS AF: 0.247 AC: 861 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	-0.90
Cadd	Benign	0.036
Dann	Benign	0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs412768; hg19: chr14-23866713; COSMIC: COSV62448801; COSMIC: COSV62448801;