rs2011488

Positions:

• 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:):

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/exons	MANE	Protein	UniProt
MYH4	NM_017533.2	c.-39-544G>T		intron_variant		ENST00000255381.2	NP_060003.2
MYHAS	NR_125367.1	n.167+61090C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH4	ENST00000255381.2	c.-39-544G>T		intron_variant		1	NM_017533.2	ENSP00000255381.2
ENSG00000272736	ENST00000399342.6	n.206+61051C>A		intron_variant		3
ENSG00000272736	ENST00000581304.1	n.143+61090C>A		intron_variant		3
MYHAS	ENST00000587182.2	n.155+61090C>A		intron_variant		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;