rs8082669

Variant names:

• chr17-10514550-G-A
• rs8082669
• NM_005963.4:c.533+318C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-10514550-G-A
• chr17-10514550-G-C

Variant summary

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

The NM_005963.4(MYH1):​c.533+318C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,986 control chromosomes in the GnomAD database, including 13,853 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 0.41 (13853 hom., cov: 32)
• Consequence: MYH1 NM_005963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 2 publications found

Genes affected

MYH1 (HGNC:7567): (myosin heavy chain 1) Myosin is a major contractile protein which converts chemical energy into mechanical energy through the hydrolysis of ATP. Myosin is a hexameric protein composed of a pair of myosin heavy chains (MYH) and two pairs of nonidentical light chains. Myosin heavy chains are encoded by a multigene family. In mammals at least 10 different myosin heavy chain (MYH) isoforms have been described from striated, smooth, and nonmuscle cells. These isoforms show expression that is spatially and temporally regulated during development. [provided by RefSeq, Jul 2008]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH1	NM_005963.4	c.533+318C>T		intron_variant	Intron 6 of 39	ENST00000226207.6	NP_005954.3
MYHAS	NR_125367.1	n.168-52987G>A		intron_variant	Intron 2 of 10
MYH1	XM_017024675.2	c.533+318C>T		intron_variant	Intron 6 of 39		XP_016880164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH1	ENST00000226207.6	c.533+318C>T		intron_variant	Intron 6 of 39	5	NM_005963.4	ENSP00000226207.5

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62722 AN: 151866 Hom.: 13835 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.407

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.413 AC: 62792 AN: 151986 Hom.: 13853 Cov.: 32 AF XY: 0.426 AC XY: 31614 AN XY: 74276

African (AFR) AF: 0.395 AC: 16381 AN: 41450

American (AMR) AF: 0.471 AC: 7186 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1380 AN: 3468

East Asian (EAS) AF: 0.856 AC: 4426 AN: 5172

South Asian (SAS) AF: 0.617 AC: 2969 AN: 4812

European-Finnish (FIN) AF: 0.437 AC: 4614 AN: 10562

Middle Eastern (MID) AF: 0.410 AC: 119 AN: 290

European-Non Finnish (NFE) AF: 0.361 AC: 24512 AN: 67962

Other (OTH) AF: 0.392 AC: 829 AN: 2114

Alfa AF: 0.394 Hom.: 2456

Bravo AF: 0.412

Asia WGS AF: 0.686 AC: 2381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.37
PhyloP100		0.016
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: rs8082669; hg19: chr17-10417867;