Variant rs8022522 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_002471.4(MYH6):c.4359+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,611,892 control chromosomes in the GnomAD database, including 119,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 17833 hom., cov: 32)

Exomes 𝑓: 0.36 ( 101239 hom. )

Consequence

MYH6
NM_002471.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.48

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 -16 ACMG points.

BP6

Variant 14-23388142-G-A is Benign according to our data. Variant chr14-23388142-G-A is described in ClinVar as [Benign]. Clinvar id is 44510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23388142-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH6	NM_002471.4 linkuse as main transcript	c.4359+13C>T		intron_variant		ENST00000405093.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH6	ENST00000405093.9 linkuse as main transcript	c.4359+13C>T		intron_variant		5	NM_002471.4	P1

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68190

AN:

151882

Hom.:

17787

Cov.:

show subpopulations

Gnomad AFR

AF:

0.731

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.343

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.450

GnomAD3 exomes

AF:

0.344

AC:

86318

AN:

250876

Hom.:

16858

AF XY:

0.343

AC XY:

46536

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.737

Gnomad AMR exome

AF:

0.232

Gnomad ASJ exome

AF:

0.417

Gnomad EAS exome

AF:

0.164

Gnomad SAS exome

AF:

0.340

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.361

GnomAD4 exome

AF:

0.364

AC:

531374

AN:

1459892

Hom.:

101239

Cov.:

AF XY:

0.362

AC XY:

262719

AN XY:

726240

show subpopulations

Gnomad4 AFR exome

AF:

0.736

Gnomad4 AMR exome

AF:

0.246

Gnomad4 ASJ exome

AF:

0.411

Gnomad4 EAS exome

AF:

0.147

Gnomad4 SAS exome

AF:

0.340

Gnomad4 FIN exome

AF:

0.268

Gnomad4 NFE exome

AF:

0.370

Gnomad4 OTH exome

AF:

0.373

GnomAD4 genome

AF:

0.449

AC:

68295

AN:

152000

Hom.:

17833

Cov.:

AF XY:

0.441

AC XY:

32754

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.731

Gnomad4 AMR

AF:

0.343

Gnomad4 ASJ

AF:

0.422

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.271

Gnomad4 NFE

AF:

0.361

Gnomad4 OTH

AF:

0.457

Alfa

AF:

0.384

Hom.:

12463

Bravo

AF:

0.466

Asia WGS

AF:

0.317

AC:

1101

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 27, 2011	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Hypertrophic cardiomyopathy 14

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

8.7

Dann

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.35

Position offset: 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