17-10504239-A-G

Variant names:

• chr17-10504239-A-G
• rs2320950
• NM_005963.4:c.2691+571T>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.2691+571T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,034 control chromosomes in the GnomAD database, including 11,122 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 0.37 (11122 hom., cov: 32)
• Consequence: MYH1 NM_005963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005963.4. 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
	MYH1	NM_005963.4	MANE Select	c.2691+571T>C		intron	N/A	NP_005954.3
	MYHAS	NR_125367.1		n.168-63298A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH1	ENST00000226207.6	TSL:5 MANE Select	c.2691+571T>C		intron	N/A	ENSP00000226207.5
	MYHAS	ENST00000399342.6	TSL:3	n.207-29085A>G		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.144-29085A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55539 AN: 151916 Hom.: 11122 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.365 AC: 55561 AN: 152034 Hom.: 11122 Cov.: 32 AF XY: 0.377 AC XY: 28045 AN XY: 74300

African (AFR) AF: 0.258 AC: 10712 AN: 41496

American (AMR) AF: 0.447 AC: 6826 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3470

East Asian (EAS) AF: 0.815 AC: 4217 AN: 5172

South Asian (SAS) AF: 0.516 AC: 2485 AN: 4820

European-Finnish (FIN) AF: 0.428 AC: 4517 AN: 10558

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.358 AC: 24301 AN: 67936

Other (OTH) AF: 0.330 AC: 696 AN: 2106

Alfa AF: 0.352 Hom.: 1590

Bravo AF: 0.361

Asia WGS AF: 0.596 AC: 2068 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.0
DANN	Benign	0.80
PhyloP100		1.0
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: rs2320950; hg19: chr17-10407556; COSMIC: COSV56845668;