rs201494323

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020884.7(MYH7B):c.-90C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00064 in 1,576,972 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00090 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00061 ( 8 hom. )

Consequence

MYH7B
NM_020884.7 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.343

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006734729).

BP6

Variant 20-34977663-C-T is Benign according to our data. Variant chr20-34977663-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 737406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000903 (136/150536) while in subpopulation SAS AF= 0.00298 (14/4694). AF 95% confidence interval is 0.0018. There are 0 homozygotes in gnomad4. There are 67 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 136 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7B	NM_020884.7 link	c.-90C>T		5_prime_UTR_variant	Exon 4 of 45	ENST00000262873.13	NP_065935.4	A7E2Y1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH7B	ENST00000262873 link	c.-90C>T	5_prime_UTR_variant	Exon 4 of 45	1	NM_020884.7	ENSP00000262873.8	A0A6E1W127
MYH7B	ENST00000673749.1 link	n.445C>T	non_coding_transcript_exon_variant	Exon 4 of 9
MYH7B	ENST00000470929.5 link	n.-4C>T	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000904

AC:

136

AN:

150404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00113

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00298

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000384

Gnomad OTH

AF:

0.000970

GnomAD3 exomes

AF:

0.00123

AC:

250

AN:

202672

Hom.:

AF XY:

0.00136

AC XY:

147

AN XY:

108452

show subpopulations

Gnomad AFR exome

AF:

0.00153

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00309

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00399

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000502

Gnomad OTH exome

AF:

0.00175

GnomAD4 exome

AF:

0.000612

AC:

873

AN:

1426436

Hom.:

Cov.:

AF XY:

0.000683

AC XY:

482

AN XY:

705988

show subpopulations

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00214

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00363

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000259

Gnomad4 OTH exome

AF:

0.000967

GnomAD4 genome

AF:

0.000903

AC:

136

AN:

150536

Hom.:

Cov.:

AF XY:

0.000912

AC XY:

AN XY:

73502

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00112

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00298

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000384

Gnomad4 OTH

AF:

0.000960

Alfa

AF:

0.000735

Hom.:

Bravo

AF:

0.00107

ESP6500AA

AF:

0.00225

AC:

ESP6500EA

AF:

0.000480

AC:

ExAC

AF:

0.00115

AC:

137

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYH7B: BP4 -

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

MYH7B-related disorder

Benign:1

Jul 18, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.011

Eigen_PC

Benign

-0.014

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.53

T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.0067

T;T

MetaSVM

Benign

-0.42

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.080

N;.

REVEL

Benign

0.21

Sift

Pathogenic

0.0

D;.

Vest4

0.20

MVP

0.56

MPC

0.52

ClinPred

0.047

GERP RS

1.4

Varity_R

0.081

gMVP

0.55

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

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