X-149485920-C-T

Variant names:

• chrX-149485920-C-T
• rs530501
• NM_000202.8:c.1180+1005G>A

Variant summary

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

The NM_000202.8(IDS):​c.1180+1005G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 110,637 control chromosomes in the GnomAD database, including 7,307 homozygotes. There are 12,944 hemizygotes in GnomAD. 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 0.41 (7307 hom., 12944 hem., cov: 23)
• Consequence: IDS NM_000202.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

Genes affected

IDS (HGNC:5389): (iduronate 2-sulfatase) This gene encodes a member of the sulfatase family of proteins. The encoded preproprotein is proteolytically processed to generate two polypeptide chains. This enzyme is involved in the lysosomal degradation of heparan sulfate and dermatan sulfate. Mutations in this gene are associated with the X-linked lysosomal storage disease mucopolysaccharidosis type II, also known as Hunter syndrome. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ENSG00000241489 (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 (NFE) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDS	NM_000202.8	c.1180+1005G>A		intron_variant	Intron 8 of 8	ENST00000340855.11	NP_000193.1
IDS	NM_001166550.4	c.910+1005G>A		intron_variant	Intron 8 of 8		NP_001160022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDS	ENST00000340855.11	c.1180+1005G>A		intron_variant	Intron 8 of 8	1	NM_000202.8	ENSP00000339801.6
ENSG00000241489	ENST00000651111.1	c.547+1005G>A		intron_variant	Intron 13 of 13			ENSP00000498395.1
ENSG00000241489	ENST00000422081.6	c.547+1005G>A		intron_variant	Intron 8 of 8	2		ENSP00000477056.1
ENSG00000241489	ENST00000441880.1	n.287+1005G>A		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 45034 AN: 110586 Hom.: 7317 Cov.: 23 AF XY: 0.393 AC XY: 12938 AN XY: 32888

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.0180

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.600

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.407 AC: 45019 AN: 110637 Hom.: 7307 Cov.: 23 AF XY: 0.393 AC XY: 12944 AN XY: 32949

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.426

Alfa AF: 0.480 Hom.: 38418

Bravo AF: 0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.64

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: rs530501; hg19: chrX-148567451;