Variant rs6815946 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000203.5(IDUA):c.543T>C(p.Asn181=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,613,002 control chromosomes in the GnomAD database, including 23,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2398 hom., cov: 33)

Exomes 𝑓: 0.16 ( 20855 hom. )

Consequence

IDUA
NM_000203.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -1.19

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 4-1001517-T-C is Benign according to our data. Variant chr4-1001517-T-C is described in ClinVar as [Benign]. Clinvar id is 92645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-1001517-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.19 with no splicing effect.

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.543T>C	p.Asn181=	synonymous_variant	5/14	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.543T>C	p.Asn181=	synonymous_variant	5/14	2	NM_000203.5	ENSP00000425081	P1	P35475-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26368

AN:

152000

Hom.:

2402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.182

GnomAD3 exomes

AF:

0.173

AC:

43316

AN:

250892

Hom.:

4280

AF XY:

0.181

AC XY:

24586

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.0788

Gnomad ASJ exome

AF:

0.160

Gnomad EAS exome

AF:

0.213

Gnomad SAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.162

AC:

237274

AN:

1460884

Hom.:

20855

Cov.:

AF XY:

0.167

AC XY:

121007

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.0844

Gnomad4 ASJ exome

AF:

0.161

Gnomad4 EAS exome

AF:

0.171

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.152

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.168

GnomAD4 genome

AF:

0.173

AC:

26365

AN:

152118

Hom.:

2398

Cov.:

AF XY:

0.173

AC XY:

12899

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.199

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.153

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.157

Hom.:

3058

Bravo

AF:

0.171

Asia WGS

AF:

0.246

AC:

859

AN:

3478

EpiCase

AF:

0.159

EpiControl

AF:

0.165

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 02, 2017	- -

Mucopolysaccharidosis type 1

Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	May 11, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 02, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

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

-0.66

CADD

Benign

0.60

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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