rs11906160

Variant names:

• chr20-34977952-G-A
• rs11906160
• NM_020884.7:c.-54G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-34977952-G-A
• chr20-34977952-G-T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: -3.94
• Publications: 51 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MYH7B	NM_020884.7	c.-54G>A		5_prime_UTR_variant	Exon 5 of 45	ENST00000262873.13	NP_065935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH7B	ENST00000262873.13	c.-54G>A		5_prime_UTR_variant	Exon 5 of 45	1	NM_020884.7	ENSP00000262873.8
MYH7B	ENST00000470929.5	n.33G>A		non_coding_transcript_exon_variant	Exon 2 of 6	2
MYH7B	ENST00000673749.1	n.481G>A		non_coding_transcript_exon_variant	Exon 5 of 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

GnomAD2 exomes AF: 0.123 AC: 30555 AN: 249176 AF XY: 0.125

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 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

African (AFR) AF: 0.267 AC: 8931 AN: 33478

American (AMR) AF: 0.0709 AC: 3171 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 2721 AN: 26134

East Asian (EAS) AF: 0.0718 AC: 2849 AN: 39700

South Asian (SAS) AF: 0.154 AC: 13299 AN: 86254

European-Finnish (FIN) AF: 0.141 AC: 7509 AN: 53074

Middle Eastern (MID) AF: 0.131 AC: 753 AN: 5756

European-Non Finnish (NFE) AF: 0.105 AC: 116466 AN: 1111938

Other (OTH) AF: 0.119 AC: 7157 AN: 60386

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

African (AFR) AF: 0.264 AC: 10950 AN: 41466

American (AMR) AF: 0.100 AC: 1532 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3468

East Asian (EAS) AF: 0.0826 AC: 427 AN: 5168

South Asian (SAS) AF: 0.138 AC: 666 AN: 4820

European-Finnish (FIN) AF: 0.146 AC: 1549 AN: 10584

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7485 AN: 67960

Other (OTH) AF: 0.129 AC: 273 AN: 2110

Alfa AF: 0.122 Hom.: 4695

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MYH7B-related disorder Benign:1

Dec 20, 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
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
PhyloP100		-3.9
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
PromoterAI		-0.025	Neutral
Varity_R		0.014
gMVP		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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