rs3761143

Variant names:

• chr20-34957942-C-T
• rs3761143
• NM_020884.7:c.-336-156C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020884.7(MYH7B):​c.-336-156C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,148 control chromosomes in the GnomAD database, including 31,424 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31424 hom., cov: 33)
• Consequence: MYH7B NM_020884.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7B	NM_020884.7	c.-336-156C>T		intron_variant	Intron 1 of 44	ENST00000262873.13	NP_065935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH7B	ENST00000262873.13	c.-336-156C>T		intron_variant	Intron 1 of 44	1	NM_020884.7	ENSP00000262873.8
MYH7B	ENST00000673749.1	n.199-156C>T		intron_variant	Intron 1 of 8

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95999 AN: 152030 Hom.: 31395 Cov.: 33

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.585

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.631 AC: 96062 AN: 152148 Hom.: 31424 Cov.: 33 AF XY: 0.628 AC XY: 46727 AN XY: 74368

African (AFR) AF: 0.794 AC: 32976 AN: 41542

American (AMR) AF: 0.446 AC: 6812 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2111 AN: 3472

East Asian (EAS) AF: 0.450 AC: 2326 AN: 5164

South Asian (SAS) AF: 0.704 AC: 3393 AN: 4818

European-Finnish (FIN) AF: 0.583 AC: 6168 AN: 10586

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40432 AN: 67976

Other (OTH) AF: 0.589 AC: 1245 AN: 2112

Alfa AF: 0.575 Hom.: 5386

Bravo AF: 0.620

Asia WGS AF: 0.598 AC: 2083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		-0.089

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3761143; hg19: chr20-33545745;