20-34957252-G-A

Variant names:

• chr20-34957252-G-A
• rs13041792
• NM_020884.7:c.-336-846G>A

Variant summary

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

The ENST00000262873.13(MYH7B):​c.-336-846G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,082 control chromosomes in the GnomAD database, including 2,841 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 0.19 (2841 hom., cov: 32)
• Consequence: MYH7B ENST00000262873.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 18 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000262873.13. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7B	NM_020884.7	MANE Select	c.-336-846G>A		intron	N/A	NP_065935.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7B	ENST00000262873.13	TSL:1 MANE Select	c.-336-846G>A		intron	N/A	ENSP00000262873.8
	MYH7B	ENST00000673749.1		n.199-846G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28923 AN: 151964 Hom.: 2838 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.190 AC: 28937 AN: 152082 Hom.: 2841 Cov.: 32 AF XY: 0.191 AC XY: 14172 AN XY: 74354

African (AFR) AF: 0.174 AC: 7212 AN: 41456

American (AMR) AF: 0.161 AC: 2454 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3468

East Asian (EAS) AF: 0.140 AC: 725 AN: 5162

South Asian (SAS) AF: 0.264 AC: 1275 AN: 4826

European-Finnish (FIN) AF: 0.206 AC: 2178 AN: 10594

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13318 AN: 67984

Other (OTH) AF: 0.207 AC: 435 AN: 2104

Alfa AF: 0.185 Hom.: 588

Bravo AF: 0.186

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.28

Splicing

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

Other links and lift over

dbSNP: rs13041792; hg19: chr20-33545055;