rs3761144

Positions:

• chr20-34956272-C-G
• chr20-34956272-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020884.7(MYH7B):​c.-337+265C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,936 control chromosomes in the GnomAD database, including 30,469 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 0.62 (30469 hom., cov: 31)
• Consequence: MYH7B NM_020884.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH7B	NM_020884.7	c.-337+265C>G		intron_variant		ENST00000262873.13	NP_065935.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH7B	ENST00000262873.13	c.-337+265C>G		intron_variant		1	NM_020884.7	ENSP00000262873	P1
MYH7B	ENST00000673749.1	n.198+265C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94746 AN: 151818 Hom.: 30440 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.624 AC: 94806 AN: 151936 Hom.: 30469 Cov.: 31 AF XY: 0.621 AC XY: 46106 AN XY: 74264

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.604

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.585

Alfa AF: 0.519 Hom.: 1565

Bravo AF: 0.611

Asia WGS AF: 0.596 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3761144; hg19: chr20-33544075;