Variant rs3755956 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.300-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,451,130 control chromosomes in the GnomAD database, including 1,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 125 hom., cov: 34)

Exomes 𝑓: 0.039 ( 1220 hom. )

Consequence

IDUA
NM_000203.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.77

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:

IDUA (HGNC:):

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=-0.87).

BP6

Variant 4-1000568-C-T is Benign according to our data. Variant chr4-1000568-C-T is described in ClinVar as [Benign]. Clinvar id is 255526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDUA	NM_000203.5 linkuse as main transcript	c.300-44C>T		intron_variant		ENST00000514224.2	NP_000194.2	P35475-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDUA	ENST00000514224.2 linkuse as main transcript	c.300-44C>T		intron_variant		2	NM_000203.5	ENSP00000425081.2		P35475-1

Frequencies

GnomAD3 genomes

AF:

0.0323

AC:

4915

AN:

152238

Hom.:

124

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0110

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0327

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.0490

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0377

Gnomad OTH

AF:

0.0507

GnomAD3 exomes

AF:

0.0372

AC:

9248

AN:

248650

Hom.:

261

AF XY:

0.0361

AC XY:

4877

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.00949

Gnomad AMR exome

AF:

0.0199

Gnomad ASJ exome

AF:

0.0155

Gnomad EAS exome

AF:

0.119

Gnomad SAS exome

AF:

0.0136

Gnomad FIN exome

AF:

0.0516

Gnomad NFE exome

AF:

0.0385

Gnomad OTH exome

AF:

0.0385

GnomAD4 exome

AF:

0.0385

AC:

50030

AN:

1298774

Hom.:

1220

Cov.:

AF XY:

0.0376

AC XY:

24643

AN XY:

654688

show subpopulations

Gnomad4 AFR exome

AF:

0.00954

Gnomad4 AMR exome

AF:

0.0209

Gnomad4 ASJ exome

AF:

0.0137

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.0137

Gnomad4 FIN exome

AF:

0.0531

Gnomad4 NFE exome

AF:

0.0392

Gnomad4 OTH exome

AF:

0.0404

GnomAD4 genome

AF:

0.0323

AC:

4919

AN:

152356

Hom.:

125

Cov.:

AF XY:

0.0327

AC XY:

2433

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.0327

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.0490

Gnomad4 NFE

AF:

0.0377

Gnomad4 OTH

AF:

0.0544

Alfa

AF:

0.0313

Hom.:

Bravo

AF:

0.0315

Asia WGS

AF:

0.0730

AC:

254

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Mucopolysaccharidosis type 1

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Apr 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.42

DANN

Benign

0.53

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