17-10451657-T-C

Variant names:

• chr17-10451657-T-C
• rs2058101
• NM_017533.2:c.3739-205A>G

Variant summary

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

The NM_017533.2(MYH4):​c.3739-205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,042 control chromosomes in the GnomAD database, including 10,778 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 0.36 (10778 hom., cov: 32)
• Consequence: MYH4 NM_017533.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.13

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH4	NM_017533.2	c.3739-205A>G		intron_variant	Intron 27 of 39	ENST00000255381.2	NP_060003.2
MYH4	XM_017024676.2	c.3739-205A>G		intron_variant	Intron 25 of 37		XP_016880165.1
MYHAS	NR_125367.1	n.167+45419T>C		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH4	ENST00000255381.2	c.3739-205A>G		intron_variant	Intron 27 of 39	1	NM_017533.2	ENSP00000255381.2
ENSG00000272736	ENST00000399342.6	n.206+45380T>C		intron_variant	Intron 2 of 3	3
ENSG00000272736	ENST00000581304.1	n.143+45419T>C		intron_variant	Intron 2 of 3	3
MYHAS	ENST00000587182.2	n.155+45419T>C		intron_variant	Intron 2 of 10	5

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54120 AN: 151924 Hom.: 10780 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.356 AC: 54142 AN: 152042 Hom.: 10778 Cov.: 32 AF XY: 0.368 AC XY: 27341 AN XY: 74304

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.320

Alfa AF: 0.230 Hom.: 521

Bravo AF: 0.350

Asia WGS AF: 0.592 AC: 2055 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.36

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: rs2058101; hg19: chr17-10354974;