20-34994152-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_020884.7(MYH7B):c.2451G>A(p.Ala817Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,612,340 control chromosomes in the GnomAD database, including 152,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12856 hom., cov: 34)

Exomes 𝑓: 0.43 ( 139658 hom. )

Consequence

MYH7B
NM_020884.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.820

Publications

27 publications found

Variant links:

Genes affected

MYH7B (HGNC:15906): (myosin heavy chain 7B) The myosin II molecule is a multi-subunit complex consisting of two heavy chains and four light chains. This gene encodes a heavy chain of myosin II, which is a member of the motor-domain superfamily. The heavy chain includes a globular motor domain, which catalyzes ATP hydrolysis and interacts with actin, and a tail domain in which heptad repeat sequences promote dimerization by interacting to form a rod-like alpha-helical coiled coil. This heavy chain subunit is a slow-twitch myosin. Alternatively spliced transcript variants have been found, but the full-length nature of these variants is not determined. [provided by RefSeq, Mar 2010]

MYH7B Gene-Disease associations (from GenCC):

left ventricular noncompaction
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MYH7B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 20-34994152-G-A is Benign according to our data. Variant chr20-34994152-G-A is described in CliVar as Benign. Clinvar id is 510873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-34994152-G-A is described in CliVar as Benign. Clinvar id is 510873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-34994152-G-A is described in CliVar as Benign. Clinvar id is 510873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-34994152-G-A is described in CliVar as Benign. Clinvar id is 510873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-34994152-G-A is described in CliVar as Benign. Clinvar id is 510873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7B	NM_020884.7 link	c.2451G>A	p.Ala817Ala	synonymous_variant	Exon 27 of 45	ENST00000262873.13	NP_065935.4	A7E2Y1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH7B	ENST00000262873.13 link	c.2451G>A	p.Ala817Ala	synonymous_variant	Exon 27 of 45	1	NM_020884.7	ENSP00000262873.8		A0A6E1W127

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59609

AN:

152088

Hom.:

12831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.546

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.439

Gnomad OTH

AF:

0.429

GnomAD2 exomes

AF:

0.448

AC:

111056

AN:

247938

AF XY:

0.435

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.718

Gnomad ASJ exome

AF:

0.385

Gnomad EAS exome

AF:

0.516

Gnomad FIN exome

AF:

0.461

Gnomad NFE exome

AF:

0.430

Gnomad OTH exome

AF:

0.453

GnomAD4 exome

AF:

0.431

AC:

628969

AN:

1460134

Hom.:

139658

Cov.:

AF XY:

0.427

AC XY:

309922

AN XY:

726198

show subpopulations

African (AFR)

AF:

0.204

AC:

6831

AN:

33458

American (AMR)

AF:

0.700

AC:

31294

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

10025

AN:

26128

East Asian (EAS)

AF:

0.558

AC:

22136

AN:

39664

South Asian (SAS)

AF:

0.301

AC:

25946

AN:

86230

European-Finnish (FIN)

AF:

0.460

AC:

24158

AN:

52530

Middle Eastern (MID)

AF:

0.406

AC:

2340

AN:

5766

European-Non Finnish (NFE)

AF:

0.433

AC:

480802

AN:

1111322

Other (OTH)

AF:

0.422

AC:

25437

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

20048

40096

60145

80193

100241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14610

29220

43830

58440

73050

<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:

0.392

AC:

59658

AN:

152206

Hom.:

12856

Cov.:

AF XY:

0.395

AC XY:

29406

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.218

AC:

9047

AN:

41536

American (AMR)

AF:

0.563

AC:

8613

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

1368

AN:

3472

East Asian (EAS)

AF:

0.546

AC:

2828

AN:

5178

South Asian (SAS)

AF:

0.305

AC:

1470

AN:

4826

European-Finnish (FIN)

AF:

0.469

AC:

4962

AN:

10588

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.439

AC:

29863

AN:

67988

Other (OTH)

AF:

0.424

AC:

896

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1847

3694

5542

7389

9236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<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:

0.419

Hom.:

37112

Bravo

AF:

0.399

Asia WGS

AF:

0.400

AC:

1390

AN:

3478

EpiCase

AF:

0.438

EpiControl

AF:

0.435

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Dec 27, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

MYH7B-related disorder

Benign:1

Jun 10, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

-0.82

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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