Variant 14-23399076-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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 (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.22 ( 4079 hom., cov: 31)

Exomes 𝑓: 0.24 ( 45035 hom. )

Consequence

MYH6
NM_002471.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0950

Variant links:

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]

MYH6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
MYH6	NM_002471.4 link	c.1582-39C>T		intron_variant	Intron 14 of 38	ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9 link	c.1582-39C>T		intron_variant	Intron 14 of 38	5	NM_002471.4	ENSP00000386041.3		P13533

Frequencies

GnomAD3 genomes

AF:

0.225

AC:

34122

AN:

151824

Hom.:

4081

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.243

AC XY:

175981

AN XY:

725090

show subpopulations

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.:

AF XY:

0.222

AC XY:

16516

AN XY:

74270

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.81

CADD

Benign

2.5

DANN

Benign

0.64

BranchPoint Hunter

2.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over