rs115134980

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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:7

Conservation

PhyloP100: -3.42

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

mucopolysaccharidosis type 1
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Myriad Women’s Health
Scheie syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Orphanet
Hurler syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
Hurler-Scheie syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

IDUA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 VariationId 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	Effect	Exon rank	MANE	Protein
IDUA	NM_000203.5 link	c.1402+36T>C	intron_variant	Intron 9 of 13	ENST00000514224.2	NP_000194.2
IDUA	NM_001363576.1 link	c.1006+36T>C	intron_variant	Intron 8 of 12		NP_001350505.1
IDUA	NR_110313.1 link	n.1490+36T>C	intron_variant	Intron 9 of 13
IDUA	XM_047415650.1 link	c.1402+36T>C	intron_variant	Intron 9 of 11		XP_047271606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDUA	ENST00000514224.2 link	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.:

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

GnomAD2 exomes

AF:

0.157

AC:

5479

AN:

34990

AF XY:

0.169

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 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

African (AFR)

AF:

0.220

AC:

5436

AN:

24710

American (AMR)

AF:

0.0888

AC:

1316

AN:

14828

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

2973

AN:

18962

East Asian (EAS)

AF:

0.157

AC:

4352

AN:

27658

South Asian (SAS)

AF:

0.291

AC:

16925

AN:

58144

European-Finnish (FIN)

AF:

0.175

AC:

5330

AN:

30434

Middle Eastern (MID)

AF:

0.201

AC:

961

AN:

4790

European-Non Finnish (NFE)

AF:

0.152

AC:

153171

AN:

1009998

Other (OTH)

AF:

0.168

AC:

8551

AN:

51022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

9325

18650

27975

37300

46625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5916

11832

17748

23664

29580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.175

AC:

26496

AN:

151630

Hom.:

2402

Cov.:

AF XY:

0.176

AC XY:

13040

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.213

AC:

8806

AN:

41372

American (AMR)

AF:

0.124

AC:

1888

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.166

AC:

576

AN:

3464

East Asian (EAS)

AF:

0.200

AC:

1020

AN:

5098

South Asian (SAS)

AF:

0.301

AC:

1445

AN:

4798

European-Finnish (FIN)

AF:

0.165

AC:

1737

AN:

10516

Middle Eastern (MID)

AF:

0.229

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.154

AC:

10413

AN:

67794

Other (OTH)

AF:

0.184

AC:

388

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1142

2283

3425

4566

5708

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

DANN

Benign

0.11

PhyloP100

-3.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over