chr20-34957252-G-A

Position:

• chr20-34957252-G-A

Variant summary

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

The NM_020884.7(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 NM_020884.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH7B	NM_020884.7	c.-336-846G>A		intron_variant		ENST00000262873.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH7B	ENST00000262873.13	c.-336-846G>A		intron_variant		1	NM_020884.7	P1
MYH7B	ENST00000673749.1	n.199-846G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.207

Alfa AF: 0.183 Hom.: 489

Bravo AF: 0.186

Asia WGS AF: 0.222 AC: 774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13041792; hg19: chr20-33545055;