rs115134980

Variant names:

• chr4-1002980-T-C
• rs115134980
• NM_000203.5:c.1402+36T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-1002980-T-C
• chr4-1002980-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000203.5(IDUA):​c.1402+36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,392,176 control chromosomes in the GnomAD database, including 19,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2402 hom., cov: 33)
  • Exomes 𝑓: 0.16 (17050 hom.)
• Consequence: IDUA NM_000203.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -3.42

Genes affected

IDUA (HGNC:5391): (alpha-L-iduronidase) This gene encodes an enzyme that hydrolyzes the terminal alpha-L-iduronic acid residues of two glycosaminoglycans, dermatan sulfate and heparan sulfate. This hydrolysis is required for the lysosomal degradation of these glycosaminoglycans. Mutations in this gene that result in enzymatic deficiency lead to the autosomal recessive disease mucopolysaccharidosis type I (MPS I). [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-1002980-T-C is Benign according to our data. Variant chr4-1002980-T-C is described in ClinVar as [Benign]. Clinvar id is 255522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDUA	NM_000203.5	c.1402+36T>C		intron_variant	Intron 9 of 13	ENST00000514224.2	NP_000194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDUA	ENST00000514224.2	c.1402+36T>C		intron_variant	Intron 9 of 13	2	NM_000203.5	ENSP00000425081.2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26500 AN: 151524 Hom.: 2406 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.185

GnomAD2 exomes AF: 0.157 AC: 5479 AN: 34990 AF XY: 0.169

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.0620

Gnomad ASJ exome AF: 0.132

Gnomad EAS exome AF: 0.196

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.160 AC: 199015 AN: 1240546 Hom.: 17050 Cov.: 36 AF XY: 0.163 AC XY: 98716 AN XY: 605004

Gnomad4 AFR exome AF: 0.220 AC: 5436 AN: 24710

Gnomad4 AMR exome AF: 0.0888 AC: 1316 AN: 14828

Gnomad4 ASJ exome AF: 0.157 AC: 2973 AN: 18962

Gnomad4 EAS exome AF: 0.157 AC: 4352 AN: 27658

Gnomad4 SAS exome AF: 0.291 AC: 16925 AN: 58144

Gnomad4 FIN exome AF: 0.175 AC: 5330 AN: 30434

Gnomad4 NFE exome AF: 0.152 AC: 153171 AN: 1009998

Gnomad4 Remaining exome AF: 0.168 AC: 8551 AN: 51022

GnomAD4 genome AF: 0.175 AC: 26496 AN: 151630 Hom.: 2402 Cov.: 33 AF XY: 0.176 AC XY: 13040 AN XY: 74122

Gnomad4 AFR AF: 0.213 AC: 0.212849 AN: 0.212849

Gnomad4 AMR AF: 0.124 AC: 0.123576 AN: 0.123576

Gnomad4 ASJ AF: 0.166 AC: 0.166282 AN: 0.166282

Gnomad4 EAS AF: 0.200 AC: 0.200078 AN: 0.200078

Gnomad4 SAS AF: 0.301 AC: 0.301167 AN: 0.301167

Gnomad4 FIN AF: 0.165 AC: 0.165177 AN: 0.165177

Gnomad4 NFE AF: 0.154 AC: 0.153598 AN: 0.153598

Gnomad4 OTH AF: 0.184 AC: 0.183886 AN: 0.183886

Alfa AF: 0.146 Hom.: 219

Bravo AF: 0.170

Asia WGS AF: 0.251 AC: 867 AN: 3442

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mucopolysaccharidosis, MPS-I-H/S Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mucopolysaccharidosis, MPS-I-S Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mucopolysaccharidosis type 1 Benign:1

Apr 13, 2018

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hurler syndrome Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.11
Mutation Taster		=100/0	polymorphism (auto)

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: rs115134980; hg19: chr4-996768; COSMIC: COSV56105910; COSMIC: COSV56105910;