Variant rs115134980 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.42

Variant links:

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]

IDUA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IDUA	NM_000203.5 linkuse as main transcript	c.1402+36T>C		intron_variant		ENST00000514224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDUA	ENST00000514224.2 linkuse as main transcript	c.1402+36T>C		intron_variant		2	NM_000203.5	P1	P35475-1

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26500

AN:

151524

Hom.:

2406

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.157

AC:

5479

AN:

34990

Hom.:

551

AF XY:

0.169

AC XY:

3616

AN XY:

21404

show subpopulations

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 SAS exome

AF:

0.259

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.:

AF XY:

0.163

AC XY:

98716

AN XY:

605004

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.0888

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.291

Gnomad4 FIN exome

AF:

0.175

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.175

AC:

26496

AN:

151630

Hom.:

2402

Cov.:

AF XY:

0.176

AC XY:

13040

AN XY:

74122

show subpopulations

Gnomad4 AFR

AF:

0.213

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.301

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.154

Gnomad4 OTH

AF:

0.184

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Mucopolysaccharidosis, MPS-I-H/S

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Mucopolysaccharidosis, MPS-I-S

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Mucopolysaccharidosis type 1

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Apr 13, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Hurler syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.2

DANN

Benign

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over