dbSNP rs8022522: MYH6:c.4359+13C>T (chr14-23388142-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -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:9

Conservation

PhyloP100: -2.48

Publications

9 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):

MYH-6 related congenital heart defects
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 14
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
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: NO_KNOWN Submitted by: ClinGen

MYH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 44510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002471.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH6	NM_002471.4	MANE Select	c.4359+13C>T		intron	N/A	NP_002462.2	P13533

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH6	ENST00000405093.9	TSL:5 MANE Select	c.4359+13C>T	intron	N/A	ENSP00000386041.3	P13533
MYH6	ENST00000968262.1		c.4392+13C>T	intron	N/A	ENSP00000638321.1
MYH6	ENST00000968257.1		c.4359+13C>T	intron	N/A	ENSP00000638316.1

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

GnomAD2 exomes

AF:

0.344

AC:

86318

AN:

250876

AF XY:

0.343

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 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

African (AFR)

AF:

0.736

AC:

24608

AN:

33414

American (AMR)

AF:

0.246

AC:

10994

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

10753

AN:

26134

East Asian (EAS)

AF:

0.147

AC:

5842

AN:

39698

South Asian (SAS)

AF:

0.340

AC:

29340

AN:

86172

European-Finnish (FIN)

AF:

0.268

AC:

14294

AN:

53334

Middle Eastern (MID)

AF:

0.398

AC:

1669

AN:

4190

European-Non Finnish (NFE)

AF:

0.370

AC:

411391

AN:

1111994

Other (OTH)

AF:

0.373

AC:

22483

AN:

60232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

22951

45902

68852

91803

114754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13068

26136

39204

52272

65340

<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:

0.449

AC:

68295

AN:

152000

Hom.:

17833

Cov.:

AF XY:

0.441

AC XY:

32754

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.731

AC:

30317

AN:

41454

American (AMR)

AF:

0.343

AC:

5234

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1464

AN:

3472

East Asian (EAS)

AF:

0.162

AC:

831

AN:

5140

South Asian (SAS)

AF:

0.332

AC:

1596

AN:

4814

European-Finnish (FIN)

AF:

0.271

AC:

2865

AN:

10568

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.361

AC:

24557

AN:

67960

Other (OTH)

AF:

0.457

AC:

963

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1674

3347

5021

6694

8368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<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:

0.395

Hom.:

19651

Bravo

AF:

0.466

Asia WGS

AF:

0.317

AC:

1101

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (2)

Hypertrophic cardiomyopathy 14 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

8.7

(source)

DANN

Benign

0.70

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over