20-34977952-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020884.7(MYH7B):c.-54G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,613,514 control chromosomes in the GnomAD database, including 12,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2157 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10004 hom.)
• Consequence: MYH7B NM_020884.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.94

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004963815).
• BP6: Variant 20-34977952-G-A is Benign according to our data. Variant chr20-34977952-G-A is described in ClinVar as [Benign]. Clinvar id is 1570582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH7B	NM_020884.7	c.-54G>A		5_prime_UTR_variant	5/45	ENST00000262873.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH7B	ENST00000262873.13	c.-54G>A		5_prime_UTR_variant	5/45	1	NM_020884.7	P1
MYH7B	ENST00000470929.5	n.33G>A		non_coding_transcript_exon_variant	2/6	2
MYH7B	ENST00000673749.1	n.481G>A		non_coding_transcript_exon_variant	5/9

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23361 AN: 151950 Hom.: 2150 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0832

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.127

GnomAD3 exomes AF: 0.123 AC: 30555 AN: 249176 Hom.: 2241 AF XY: 0.125 AC XY: 16870 AN XY: 135186

Gnomad AFR exome AF: 0.267

Gnomad AMR exome AF: 0.0648

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.0976

Gnomad SAS exome AF: 0.151

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.111 AC: 162856 AN: 1461444 Hom.: 10004 Cov.: 33 AF XY: 0.113 AC XY: 81866 AN XY: 727032

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.0709

Gnomad4 ASJ exome AF: 0.104

Gnomad4 EAS exome AF: 0.0718

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.154 AC: 23394 AN: 152070 Hom.: 2157 Cov.: 32 AF XY: 0.156 AC XY: 11558 AN XY: 74318

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.0826

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.129

Alfa AF: 0.115 Hom.: 2630

Bravo AF: 0.154

TwinsUK AF: 0.0960 AC: 356

ALSPAC AF: 0.105 AC: 405

ESP6500AA AF: 0.240 AC: 1039

ESP6500EA AF: 0.111 AC: 950

ExAC AF: 0.129 AC: 15608

Asia WGS AF: 0.129 AC: 446 AN: 3478

EpiCase AF: 0.112

EpiControl AF: 0.112

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

MYH7B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 20, 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
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	0.44
Dann	Benign	0.64
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.31	T;T
MetaRNN	Benign	0.0050	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.010	N;.
REVEL	Benign	0.13
Sift	Benign	0.55	T;.
Vest4		0.0060
MPC		0.45
ClinPred		0.013	T
GERP RS		-9.1
Varity_R		0.014
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

Other links and lift over

dbSNP: rs11906160; hg19: chr20-33565755; COSMIC: COSV53420686; COSMIC: COSV53420686;