rs1131853

Variant names:

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.1525-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,403,314 control chromosomes in the GnomAD database, including 35,057 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3793 hom., cov: 32)

Exomes 𝑓: 0.22 ( 31264 hom. )

Consequence

IDUA
NM_000203.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.138

Publications

4 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=-0.9).

BP6

Variant 4-1003307-T-C is Benign according to our data. Variant chr4-1003307-T-C is described in ClinVar as [Benign]. Clinvar id is 255525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IDUA	NM_000203.5 link	c.1525-38T>C		intron_variant	Intron 10 of 13	ENST00000514224.2	NP_000194.2	P35475-1
IDUA	XM_047415650.1 link	c.1674T>C	p.Ala558Ala	synonymous_variant	Exon 10 of 12		XP_047271606.1
IDUA	NM_001363576.1 link	c.1129-38T>C		intron_variant	Intron 9 of 12		NP_001350505.1
IDUA	NR_110313.1 link	n.1613-38T>C		intron_variant	Intron 10 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IDUA	ENST00000514224.2 link	c.1525-38T>C		intron_variant	Intron 10 of 13	2	NM_000203.5	ENSP00000425081.2		P35475-1

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33600

AN:

151414

Hom.:

3799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.256

GnomAD2 exomes

AF:

0.192

AC:

6640

AN:

34608

AF XY:

0.207

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.0978

Gnomad ASJ exome

AF:

0.238

Gnomad EAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.220

AC:

274963

AN:

1251794

Hom.:

31264

Cov.:

AF XY:

0.222

AC XY:

136575

AN XY:

614844

show subpopulations

African (AFR)

AF:

0.237

AC:

5785

AN:

24364

American (AMR)

AF:

0.146

AC:

2090

AN:

14318

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

5226

AN:

18942

East Asian (EAS)

AF:

0.182

AC:

5004

AN:

27492

South Asian (SAS)

AF:

0.319

AC:

19270

AN:

60344

European-Finnish (FIN)

AF:

0.188

AC:

5880

AN:

31338

Middle Eastern (MID)

AF:

0.345

AC:

1219

AN:

3536

European-Non Finnish (NFE)

AF:

0.214

AC:

218682

AN:

1020020

Other (OTH)

AF:

0.230

AC:

11807

AN:

51440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

10469

20938

31408

41877

52346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.222

AC:

33595

AN:

151520

Hom.:

3793

Cov.:

AF XY:

0.221

AC XY:

16333

AN XY:

74036

show subpopulations

African (AFR)

AF:

0.231

AC:

9550

AN:

41342

American (AMR)

AF:

0.191

AC:

2907

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

1001

AN:

3470

East Asian (EAS)

AF:

0.220

AC:

1115

AN:

5068

South Asian (SAS)

AF:

0.333

AC:

1602

AN:

4810

European-Finnish (FIN)

AF:

0.178

AC:

1866

AN:

10488

Middle Eastern (MID)

AF:

0.414

AC:

121

AN:

292

European-Non Finnish (NFE)

AF:

0.217

AC:

14708

AN:

67782

Other (OTH)

AF:

0.255

AC:

535

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1373

2746

4120

5493

6866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.207

Hom.:

421

Bravo

AF:

0.220

Asia WGS

AF:

0.295

AC:

1011

AN:

3414

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mucopolysaccharidosis type 1

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

8.0

(source)

DANN

Benign

0.21

PhyloP100

0.14

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

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rs1131853

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