Variant 14-23386269-C-G 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.4959+46G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 1,613,660 control chromosomes in the GnomAD database, including 9,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 540 hom., cov: 31)

Exomes 𝑓: 0.10 ( 8656 hom. )

Consequence

MYH6
NM_002471.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.401

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 14-23386269-C-G is Benign according to our data. Variant chr14-23386269-C-G is described in ClinVar as [Benign]. Clinvar id is 258712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH6	NM_002471.4 linkuse as main transcript	c.4959+46G>C		intron_variant		ENST00000405093.9	NP_002462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH6	ENST00000405093.9 linkuse as main transcript	c.4959+46G>C		intron_variant		5	NM_002471.4	ENSP00000386041.3		P13533

Frequencies

GnomAD3 genomes

AF:

0.0760

AC:

11566

AN:

152116

Hom.:

539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0547

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0317

Gnomad FIN

AF:

0.0904

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.0718

GnomAD3 exomes

AF:

0.0749

AC:

18709

AN:

249782

Hom.:

889

AF XY:

0.0755

AC XY:

10208

AN XY:

135154

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.0356

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0385

Gnomad FIN exome

AF:

0.0854

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.0900

GnomAD4 exome

AF:

0.102

AC:

149548

AN:

1461424

Hom.:

8656

Cov.:

AF XY:

0.101

AC XY:

73126

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.0272

Gnomad4 AMR exome

AF:

0.0373

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0395

Gnomad4 FIN exome

AF:

0.0840

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.0969

GnomAD4 genome

AF:

0.0760

AC:

11569

AN:

152236

Hom.:

540

Cov.:

AF XY:

0.0746

AC XY:

5554

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0309

Gnomad4 AMR

AF:

0.0547

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0317

Gnomad4 FIN

AF:

0.0904

Gnomad4 NFE

AF:

0.113

Gnomad4 OTH

AF:

0.0711

Alfa

AF:

0.0664

Hom.:

Bravo

AF:

0.0726

Asia WGS

AF:

0.0180

AC:

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

-0.84

CADD

Benign

1.2

DANN

Benign

0.67

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