rs439735

chr14-23399076-G-A

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.1582-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,608,864 control chromosomes in the GnomAD database, including 49,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4079 hom., cov: 31)
  • Exomes 𝑓: 0.24 (45035 hom.)
• Consequence: MYH6 NM_002471.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0950

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=-0.81).
• BP6: Variant 14-23399076-G-A is Benign according to our data. Variant chr14-23399076-G-A is described in ClinVar as [Benign]. Clinvar id is 258706.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr14-23399076-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH6	NM_002471.4	c.1582-39C>T		intron_variant		ENST00000405093.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH6	ENST00000405093.9	c.1582-39C>T		intron_variant		5	NM_002471.4	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34122 AN: 151824 Hom.: 4081 Cov.: 31

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.0658

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.227

GnomAD3 exomes AF: 0.210 AC: 52154 AN: 248560 Hom.: 6004 AF XY: 0.214 AC XY: 28824 AN XY: 134610

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.305

Gnomad EAS exome AF: 0.0664

Gnomad SAS exome AF: 0.193

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.256

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.244 AC: 355222 AN: 1456922 Hom.: 45035 Cov.: 32 AF XY: 0.243 AC XY: 175981 AN XY: 725090

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.304

Gnomad4 EAS exome AF: 0.0524

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.225 AC: 34134 AN: 151942 Hom.: 4079 Cov.: 31 AF XY: 0.222 AC XY: 16516 AN XY: 74270

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.0662

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.225

Alfa AF: 0.234 Hom.: 1363

Bravo AF: 0.219

Asia WGS AF: 0.126 AC: 438 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	-0.81
Cadd	Benign	2.5
Dann	Benign	0.64

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: rs439735; hg19: chr14-23868285;