chr17-10496580-A-G

Position:

• chr17-10496580-A-G

Variant summary

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

The NM_005963.4(MYH1):​c.4657-31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,613,346 control chromosomes in the GnomAD database, including 163,693 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 0.43 (14636 hom., cov: 31)
  • Exomes 𝑓: 0.44 (149057 hom.)
• Consequence: MYH1 NM_005963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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
MYH1	NM_005963.4	c.4657-31T>C		intron_variant		ENST00000226207.6	NP_005954.3
MYHAS	NR_125367.1	n.168-70957A>G		intron_variant, non_coding_transcript_variant
MYH1	XM_017024675.2	c.4657-31T>C		intron_variant			XP_016880164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH1	ENST00000226207.6	c.4657-31T>C		intron_variant		5	NM_005963.4	ENSP00000226207	P1
	ENST00000399342.6	n.207-36744A>G		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1	n.144-36744A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64578 AN: 151784 Hom.: 14628 Cov.: 31

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.394

GnomAD3 exomes AF: 0.500 AC: 125201 AN: 250176 Hom.: 33913 AF XY: 0.500 AC XY: 67734 AN XY: 135498

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.607

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.874

Gnomad SAS exome AF: 0.622

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.410

Gnomad OTH exome AF: 0.457

GnomAD4 exome AF: 0.441 AC: 644394 AN: 1461444 Hom.: 149057 Cov.: 41 AF XY: 0.445 AC XY: 323792 AN XY: 727076

Gnomad4 AFR exome AF: 0.319

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.461

Gnomad4 EAS exome AF: 0.843

Gnomad4 SAS exome AF: 0.620

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.408

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.425 AC: 64625 AN: 151902 Hom.: 14636 Cov.: 31 AF XY: 0.439 AC XY: 32554 AN XY: 74232

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.394

Alfa AF: 0.415 Hom.: 3958

Bravo AF: 0.419

Asia WGS AF: 0.689 AC: 2395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.5
DANN	Benign	0.69

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: rs3744563; hg19: chr17-10399897; COSMIC: COSV56845662;