Variant chr4-1003307-T-C 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.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

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=-0.9).

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/exons	MANE	Protein	UniProt
IDUA	NM_000203.5 linkuse as main transcript	c.1525-38T>C		intron_variant		ENST00000514224.2	NP_000194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IDUA	ENST00000514224.2 linkuse as main transcript	c.1525-38T>C		intron_variant		2	NM_000203.5	ENSP00000425081	P1	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

GnomAD3 exomes

AF:

0.192

AC:

6640

AN:

34608

Hom.:

788

AF XY:

0.207

AC XY:

4348

AN XY:

21016

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 SAS exome

AF:

0.269

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

Gnomad4 AFR exome

AF:

0.237

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.182

Gnomad4 SAS exome

AF:

0.319

Gnomad4 FIN exome

AF:

0.188

Gnomad4 NFE exome

AF:

0.214

Gnomad4 OTH exome

AF:

0.230

GnomAD4 genome

AF:

0.222

AC:

33595

AN:

151520

Hom.:

3793

Cov.:

AF XY:

0.221

AC XY:

16333

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.288

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.333

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.255

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 14, 2021

- -

Mucopolysaccharidosis type 1

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

8.0

DANN

Benign

0.21

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