Variant rs6811373 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.972+48A>G 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 1,570,730 control chromosomes in the GnomAD database, including 22,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2424 hom., cov: 34)

Exomes 𝑓: 0.16 ( 20025 hom. )

Consequence

IDUA
NM_000203.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.175

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=-0.89).

BP6

Variant 4-1002209-A-G is Benign according to our data. Variant chr4-1002209-A-G is described in ClinVar as [Benign]. Clinvar id is 255529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-1002209-A-G is described in Lovd as [Benign].

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.972+48A>G		intron_variant		ENST00000514224.2	NP_000194.2	P35475-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IDUA	ENST00000514224.2 linkuse as main transcript	c.972+48A>G	intron_variant		2	NM_000203.5	ENSP00000425081.2	P35475-1
IDUA	ENST00000247933.9 linkuse as main transcript	c.972+48A>G	intron_variant		1		ENSP00000247933.4	P35475-1
IDUA	ENST00000514698.5 linkuse as main transcript	n.1020A>G	non_coding_transcript_exon_variant	5/11	5
IDUA	ENST00000652070.1 linkuse as main transcript	n.1028+48A>G	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.175

AC:

26534

AN:

151786

Hom.:

2428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.175

AC:

31234

AN:

178824

Hom.:

3120

AF XY:

0.184

AC XY:

17872

AN XY:

96964

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.0817

Gnomad ASJ exome

AF:

0.162

Gnomad EAS exome

AF:

0.214

Gnomad SAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.162

AC:

229238

AN:

1418828

Hom.:

20025

Cov.:

AF XY:

0.165

AC XY:

116173

AN XY:

702020

show subpopulations

Gnomad4 AFR exome

AF:

0.229

Gnomad4 AMR exome

AF:

0.0876

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.170

GnomAD4 genome

AF:

0.175

AC:

26533

AN:

151902

Hom.:

2424

Cov.:

AF XY:

0.175

AC XY:

12968

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.165

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.157

Hom.:

376

Bravo

AF:

0.172

Asia WGS

AF:

0.248

AC:

867

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

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

-0.89

CADD

Benign

7.5

DANN

Benign

0.11

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