14-23386640-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002471.4(MYH6):c.4651-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,461,826 control chromosomes in the GnomAD database, including 53,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4408 hom., cov: 30)

Exomes 𝑓: 0.28 ( 49100 hom. )

Consequence

MYH6
NM_002471.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.10

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy 14
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine
Keppen-Lubinsky syndrome
Inheritance: AD Classification: MODERATE Submitted by: Illumina
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
atrial septal defect 3
Inheritance: AD Classification: LIMITED Submitted by: G2P
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

MYH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 14-23386640-C-T is Benign according to our data. Variant chr14-23386640-C-T is described in ClinVar as Benign. ClinVar VariationId is 258711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH6	NM_002471.4 link	c.4651-17G>A		intron_variant	Intron 32 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.4651-17G>A		intron_variant	Intron 32 of 38	5	NM_002471.4	ENSP00000386041.3

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

35818

AN:

150064

Hom.:

4403

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.280

GnomAD2 exomes

AF:

0.249

AC:

59829

AN:

240322

AF XY:

0.260

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.173

Gnomad ASJ exome

AF:

0.328

Gnomad EAS exome

AF:

0.178

Gnomad FIN exome

AF:

0.216

Gnomad NFE exome

AF:

0.264

Gnomad OTH exome

AF:

0.268

GnomAD4 exome

AF:

0.279

AC:

366391

AN:

1311638

Hom.:

49100

Cov.:

AF XY:

0.282

AC XY:

184800

AN XY:

654186

show subpopulations

African (AFR)

AF:

0.203

AC:

6097

AN:

30038

American (AMR)

AF:

0.187

AC:

7956

AN:

42556

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

8137

AN:

23336

East Asian (EAS)

AF:

0.201

AC:

6949

AN:

34650

South Asian (SAS)

AF:

0.360

AC:

29508

AN:

81986

European-Finnish (FIN)

AF:

0.242

AC:

11319

AN:

46856

Middle Eastern (MID)

AF:

0.350

AC:

1866

AN:

5332

European-Non Finnish (NFE)

AF:

0.282

AC:

279717

AN:

993224

Other (OTH)

AF:

0.277

AC:

14842

AN:

53660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

11581

23161

34742

46322

57903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9446

18892

28338

37784

47230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.239

AC:

35850

AN:

150188

Hom.:

4408

Cov.:

AF XY:

0.238

AC XY:

17506

AN XY:

73406

show subpopulations

African (AFR)

AF:

0.190

AC:

7789

AN:

41014

American (AMR)

AF:

0.243

AC:

3677

AN:

15138

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1183

AN:

3456

East Asian (EAS)

AF:

0.188

AC:

937

AN:

4996

South Asian (SAS)

AF:

0.363

AC:

1686

AN:

4642

European-Finnish (FIN)

AF:

0.222

AC:

2241

AN:

10086

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17320

AN:

67582

Other (OTH)

AF:

0.284

AC:

592

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1279

2558

3837

5116

6395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.247

Hom.:

918

Bravo

AF:

0.234

Asia WGS

AF:

0.261

AC:

908

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy 14

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.054

(source)

DANN

Benign

0.76

PhyloP100

-3.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over