Variant 20-34994152-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_020884.7(MYH7B):c.2451G>A(p.Ala817=) 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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/exons	MANE	UniProt
MYH7B	NM_020884.7 linkuse as main transcript	c.2451G>A	p.Ala817=	synonymous_variant	27/45	ENST00000262873.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH7B	ENST00000262873.13 linkuse as main transcript	c.2451G>A	p.Ala817=	synonymous_variant	27/45	1	NM_020884.7	P1

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

GnomAD3 exomes

AF:

0.448

AC:

111056

AN:

247938

Hom.:

27229

AF XY:

0.435

AC XY:

58604

AN XY:

134678

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 SAS exome

AF:

0.299

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

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.700

Gnomad4 ASJ exome

AF:

0.384

Gnomad4 EAS exome

AF:

0.558

Gnomad4 SAS exome

AF:

0.301

Gnomad4 FIN exome

AF:

0.460

Gnomad4 NFE exome

AF:

0.433

Gnomad4 OTH exome

AF:

0.422

GnomAD4 genome

AF:

0.392

AC:

59658

AN:

152206

Hom.:

12856

Cov.:

AF XY:

0.395

AC XY:

29406

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.218

Gnomad4 AMR

AF:

0.563

Gnomad4 ASJ

AF:

0.394

Gnomad4 EAS

AF:

0.546

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.469

Gnomad4 NFE

AF:

0.439

Gnomad4 OTH

AF:

0.424

Alfa

AF:

0.428

Hom.:

22181

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 27, 2017

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 10, 2019

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

DANN

Benign

0.85

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

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