rs11248061

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The NM_000203.5:c.24C>A variant in IDUA is a synonymous (silent) variant (p.Ala8=). The Grpmax Filtering AF (95% confidence) in gnomAD v4.1.0 is 0.5236 in the Admixed American population. This is higher than the ClinGen Lysosomal Diseases VCEP’s threshold for BA1 (>0.005), and therefore meets this criterion (BA1). There is a ClinVar entry for this variant (Variation ID: 92638). In summary, this variant meets the criteria to be classified as benign for mucopolysaccharidosis type 1. IDUA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (Specifications Version 1.0.0): BA1.(Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on January 2, 2025) LINK:https://erepo.genome.network/evrepo/ui/classification/CA145878/MONDO:0001586/091

Frequency

Genomes: 𝑓 0.40 ( 12365 hom., cov: 35)

Exomes 𝑓: 0.43 ( 119539 hom. )

Consequence

IDUA
NM_000203.5 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:13

Conservation

PhyloP100: -0.0790

Publications

26 publications found

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:

SLC26A1 (HGNC:10993): (solute carrier family 26 member 1) This gene is a member of a family of sulfate/anion transporter genes. Family members are well conserved in their genomic (number and size of exons) and protein (aa length among species) structures, but have markedly different tissue expression patterns. This gene is primarily expressed in the liver, pancreas, and brain. Three splice variants that encode different isoforms have been identified. [provided by RefSeq, Jul 2008]

SLC26A1 links:

DGKQ (HGNC:2856): (diacylglycerol kinase theta) The protein encoded by this gene contains three cysteine-rich domains, a proline-rich region, and a pleckstrin homology domain with an overlapping Ras-associating domain. It is localized in the speckle domains of the nucleus, and mediates the regeneration of phosphatidylinositol (PI) from diacylglycerol in the PI-cycle during cell signal transduction. [provided by RefSeq, Jul 2008]

DGKQ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000203.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IDUA	NM_000203.5	MANE Select	c.24C>A	p.Ala8Ala	synonymous	Exon 1 of 14	NP_000194.2
SLC26A1	NM_134425.4		c.576+4020G>T		intron	N/A	NP_602297.1
IDUA	NR_110313.1		n.112C>A		non_coding_transcript_exon	Exon 1 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IDUA	ENST00000514224.2	TSL:2 MANE Select	c.24C>A	p.Ala8Ala	synonymous	Exon 1 of 14	ENSP00000425081.2
IDUA	ENST00000247933.9	TSL:1	c.24C>A	p.Ala8Ala	synonymous	Exon 1 of 14	ENSP00000247933.4
SLC26A1	ENST00000398520.6	TSL:1	c.576+4020G>T		intron	N/A	ENSP00000381532.2

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60531

AN:

151804

Hom.:

12356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.404

GnomAD2 exomes

AF:

0.469

AC:

36707

AN:

78206

AF XY:

0.464

show subpopulations

Gnomad AFR exome

AF:

0.395

Gnomad AMR exome

AF:

0.585

Gnomad ASJ exome

AF:

0.388

Gnomad EAS exome

AF:

0.346

Gnomad FIN exome

AF:

0.448

Gnomad NFE exome

AF:

0.462

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.427

AC:

553283

AN:

1295012

Hom.:

119539

Cov.:

AF XY:

0.428

AC XY:

273242

AN XY:

638620

show subpopulations

African (AFR)

AF:

0.323

AC:

8460

AN:

26192

American (AMR)

AF:

0.558

AC:

13741

AN:

24642

Ashkenazi Jewish (ASJ)

AF:

0.386

AC:

8354

AN:

21652

East Asian (EAS)

AF:

0.360

AC:

9971

AN:

27712

South Asian (SAS)

AF:

0.444

AC:

30805

AN:

69342

European-Finnish (FIN)

AF:

0.429

AC:

13919

AN:

32482

Middle Eastern (MID)

AF:

0.376

AC:

1399

AN:

3718

European-Non Finnish (NFE)

AF:

0.429

AC:

444790

AN:

1036184

Other (OTH)

AF:

0.411

AC:

21844

AN:

53088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

14379

28758

43138

57517

71896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14094

28188

42282

56376

70470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.399

AC:

60566

AN:

151912

Hom.:

12365

Cov.:

AF XY:

0.403

AC XY:

29897

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.332

AC:

13757

AN:

41494

American (AMR)

AF:

0.484

AC:

7380

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

1274

AN:

3470

East Asian (EAS)

AF:

0.278

AC:

1428

AN:

5136

South Asian (SAS)

AF:

0.438

AC:

2117

AN:

4832

European-Finnish (FIN)

AF:

0.435

AC:

4578

AN:

10536

Middle Eastern (MID)

AF:

0.315

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.425

AC:

28848

AN:

67888

Other (OTH)

AF:

0.406

AC:

856

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

2060

4120

6180

8240

10300

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.401

Hom.:

1556

Bravo

AF:

0.399

Asia WGS

AF:

0.319

AC:

1100

AN:

3448

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Mucopolysaccharidosis type 1 (4)

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.7

(source)

DANN

Benign

0.59

PhyloP100

-0.079

PromoterAI

-0.082

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over