rs2011488

Variant names:

• chr17-10467328-C-A
• rs2011488
• NM_017533.2:c.-39-544G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-10467328-C-A
• chr17-10467328-C-G
• chr17-10467328-C-T

Variant summary

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

The NM_017533.2(MYH4):​c.-39-544G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,974 control chromosomes in the GnomAD database, including 12,802 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 0.39 (12802 hom., cov: 32)
• Consequence: MYH4 NM_017533.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95

Genes affected

MYH4 (HGNC:7574): (myosin heavy chain 4) Enables double-stranded RNA binding activity. Involved in muscle contraction. Located in myofibril. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000272736 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• 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
MYH4	NM_017533.2	c.-39-544G>T		intron_variant	Intron 2 of 39	ENST00000255381.2	NP_060003.2
MYHAS	NR_125367.1	n.167+61090C>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH4	ENST00000255381.2	c.-39-544G>T		intron_variant	Intron 2 of 39	1	NM_017533.2	ENSP00000255381.2
ENSG00000272736	ENST00000399342.6	n.206+61051C>A		intron_variant	Intron 2 of 3	3
ENSG00000272736	ENST00000581304.1	n.143+61090C>A		intron_variant	Intron 2 of 3	3
MYHAS	ENST00000587182.2	n.155+61090C>A		intron_variant	Intron 2 of 10	5

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59942 AN: 151856 Hom.: 12796 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.395 AC: 59989 AN: 151974 Hom.: 12802 Cov.: 32 AF XY: 0.408 AC XY: 30273 AN XY: 74266

Gnomad4 AFR AF: 0.334

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.379

Alfa AF: 0.214 Hom.: 431

Bravo AF: 0.392

Asia WGS AF: 0.679 AC: 2353 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.0
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs2011488; hg19: chr17-10370645; COSMIC: COSV55115026;