rs7147244

Positions:

• chr14-23407007-G-A
• chr14-23407007-G-C

Variant summary

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

The NM_002471.4(MYH6):​c.201+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 1,612,258 control chromosomes in the GnomAD database, including 1,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (431 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1269 hom.)
• Consequence: MYH6 NM_002471.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.21

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 14-23407007-G-A is Benign according to our data. Variant chr14-23407007-G-A is described in ClinVar as [Benign]. Clinvar id is 258708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23407007-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH6	NM_002471.4	c.201+16C>T		intron_variant		ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9	c.201+16C>T		intron_variant		5	NM_002471.4	ENSP00000386041	P1
MYH6	ENST00000557461.2	n.268+16C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8768 AN: 151924 Hom.: 428 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00688

Gnomad FIN AF: 0.00661

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0354

Gnomad OTH AF: 0.0483

GnomAD3 exomes AF: 0.0293 AC: 7361 AN: 251098 Hom.: 220 AF XY: 0.0273 AC XY: 3707 AN XY: 135750

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.0196

Gnomad ASJ exome AF: 0.0248

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00598

Gnomad FIN exome AF: 0.00701

Gnomad NFE exome AF: 0.0331

Gnomad OTH exome AF: 0.0269

GnomAD4 exome AF: 0.0360 AC: 52561 AN: 1460216 Hom.: 1269 Cov.: 31 AF XY: 0.0347 AC XY: 25228 AN XY: 726556

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.0224

Gnomad4 ASJ exome AF: 0.0262

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.00591

Gnomad4 FIN exome AF: 0.00794

Gnomad4 NFE exome AF: 0.0388

Gnomad4 OTH exome AF: 0.0337

GnomAD4 genome AF: 0.0578 AC: 8790 AN: 152042 Hom.: 431 Cov.: 32 AF XY: 0.0554 AC XY: 4115 AN XY: 74326

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0318

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00668

Gnomad4 FIN AF: 0.00661

Gnomad4 NFE AF: 0.0354

Gnomad4 OTH AF: 0.0478

Alfa AF: 0.0385 Hom.: 142

Bravo AF: 0.0640

Asia WGS AF: 0.0210 AC: 74 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Hypertrophic cardiomyopathy 14 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.041
DANN	Benign	0.50

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: rs7147244; hg19: chr14-23876216;