rs7211175

Variant names:

• chr17-10393705-C-A
• rs7211175
• NM_002472.3:c.5167-495G>T

Variant summary

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

The NM_002472.3(MYH8):​c.5167-495G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,000 control chromosomes in the GnomAD database, including 23,559 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 0.55 (23559 hom., cov: 32)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 1 publications found

Genes affected

MYH8 (HGNC:7578): (myosin heavy chain 8) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is predominantly expressed in fetal skeletal muscle. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in trismus-pseudocamptodactyly syndrome. [provided by RefSeq, Sep 2009]

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002472.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	NM_002472.3	MANE Select	c.5167-495G>T		intron	N/A	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.76+10498C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	ENST00000403437.2	TSL:5 MANE Select	c.5167-495G>T		intron	N/A	ENSP00000384330.2	P13535
	MYHAS	ENST00000399342.6	TSL:3	n.76+10498C>A		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.52+10498C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83333 AN: 151882 Hom.: 23550 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.549 AC: 83378 AN: 152000 Hom.: 23559 Cov.: 32 AF XY: 0.537 AC XY: 39859 AN XY: 74290

African (AFR) AF: 0.592 AC: 24531 AN: 41430

American (AMR) AF: 0.497 AC: 7599 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1872 AN: 3468

East Asian (EAS) AF: 0.134 AC: 695 AN: 5176

South Asian (SAS) AF: 0.341 AC: 1647 AN: 4832

European-Finnish (FIN) AF: 0.515 AC: 5440 AN: 10556

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39732 AN: 67944

Other (OTH) AF: 0.586 AC: 1238 AN: 2114

Alfa AF: 0.579 Hom.: 4323

Bravo AF: 0.553

Asia WGS AF: 0.269 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.022
DANN	Benign	0.37
PhyloP100		-2.5
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: rs7211175; hg19: chr17-10297022; COSMIC: COSV67971322;