chr20-34989186-C-G

Variant names:

• chr20-34989186-C-G
• rs1885120
• NM_020884.7:c.1588-554C>G

Variant summary

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

The NM_020884.7(MYH7B):​c.1588-554C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.957 in 152,346 control chromosomes in the GnomAD database, including 69,786 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 0.96 (69786 hom., cov: 34)
• Consequence: MYH7B NM_020884.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 36 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020884.7. 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.1588-554C>G		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.1588-554C>G		intron	N/A	ENSP00000262873.8

Frequencies

GnomAD3 genomes AF: 0.956 AC: 145601 AN: 152228 Hom.: 69727 Cov.: 34

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.994

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.923

Gnomad OTH AF: 0.969

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

GnomAD4 genome AF: 0.957 AC: 145719 AN: 152346 Hom.: 69786 Cov.: 34 AF XY: 0.960 AC XY: 71545 AN XY: 74494

African (AFR) AF: 0.987 AC: 41018 AN: 41578

American (AMR) AF: 0.972 AC: 14869 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.974 AC: 3381 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5189 AN: 5190

South Asian (SAS) AF: 0.994 AC: 4790 AN: 4820

European-Finnish (FIN) AF: 0.982 AC: 10434 AN: 10626

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.923 AC: 62789 AN: 68040

Other (OTH) AF: 0.970 AC: 2050 AN: 2114

Alfa AF: 0.946 Hom.: 8469

Bravo AF: 0.957

Asia WGS AF: 0.995 AC: 3460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.5
DANN	Benign	0.35
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1885120; hg19: chr20-33576989;