Variant 4-1001634-G-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.590-45G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,605,734 control chromosomes in the GnomAD database, including 23,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2374 hom., cov: 34)

Exomes 𝑓: 0.16 ( 20703 hom. )

Consequence

IDUA
NM_000203.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.00500

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=-0.83).

BP6

Variant 4-1001634-G-C is Benign according to our data. Variant chr4-1001634-G-C is described in ClinVar as [Benign]. Clinvar id is 255528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 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.590-45G>C		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.590-45G>C		intron_variant		2	NM_000203.5	ENSP00000425081.2		P35475-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26286

AN:

152066

Hom.:

2378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.174

AC:

42032

AN:

241784

Hom.:

4104

AF XY:

0.182

AC XY:

23992

AN XY:

131638

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.0786

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.214

Gnomad SAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.162

AC:

235950

AN:

1453550

Hom.:

20703

Cov.:

AF XY:

0.166

AC XY:

120381

AN XY:

723228

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.0842

Gnomad4 ASJ exome

AF:

0.160

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.153

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.169

GnomAD4 genome

AF:

0.173

AC:

26283

AN:

152184

Hom.:

2374

Cov.:

AF XY:

0.173

AC XY:

12863

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.153

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.101

Hom.:

207

Bravo

AF:

0.170

Asia WGS

AF:

0.249

AC:

872

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
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 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

- -

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

-0.83

CADD

Benign

0.73

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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