4-1002713-GCCC-GCCCCC

Position:

• chr4-1002713-GCCC-GCCCCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000203.5(IDUA):​c.1190-11_1190-10dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000409 in 1,363,574 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (2 hom., cov: 29)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: IDUA NM_000203.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.792

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-1002713-G-GCC is Benign according to our data. Variant chr4-1002713-G-GCC is described in ClinVar as [Benign]. Clinvar id is 1600766.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00128 (192/149760) while in subpopulation AFR AF= 0.00373 (152/40706). AF 95% confidence interval is 0.00325. There are 2 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IDUA	NM_000203.5	c.1190-11_1190-10dup		intron_variant		ENST00000514224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IDUA	ENST00000514224.2	c.1190-11_1190-10dup		intron_variant		2	NM_000203.5	P1

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 193 AN: 149662 Hom.: 2 Cov.: 29

Gnomad AFR AF: 0.00374

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000396

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000595

Gnomad SAS AF: 0.00106

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00654

Gnomad NFE AF: 0.000342

Gnomad OTH AF: 0.000978

GnomAD3 exomes AF: 0.000738 AC: 54 AN: 73188 Hom.: 0 AF XY: 0.000916 AC XY: 38 AN XY: 41468

Gnomad AFR exome AF: 0.00188

Gnomad AMR exome AF: 0.000133

Gnomad ASJ exome AF: 0.00105

Gnomad EAS exome AF: 0.00192

Gnomad SAS exome AF: 0.00150

Gnomad FIN exome AF: 0.000233

Gnomad NFE exome AF: 0.000452

Gnomad OTH exome AF: 0.000908

GnomAD4 exome AF: 0.000302 AC: 366 AN: 1213814 Hom.: 0 Cov.: 24 AF XY: 0.000333 AC XY: 200 AN XY: 601188

Gnomad4 AFR exome AF: 0.00112

Gnomad4 AMR exome AF: 0.000172

Gnomad4 ASJ exome AF: 0.000312

Gnomad4 EAS exome AF: 0.000173

Gnomad4 SAS exome AF: 0.00186

Gnomad4 FIN exome AF: 0.000122

Gnomad4 NFE exome AF: 0.000180

Gnomad4 OTH exome AF: 0.000373

GnomAD4 genome AF: 0.00128 AC: 192 AN: 149760 Hom.: 2 Cov.: 29 AF XY: 0.00123 AC XY: 90 AN XY: 73090

Gnomad4 AFR AF: 0.00373

Gnomad4 AMR AF: 0.000396

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000596

Gnomad4 SAS AF: 0.00106

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000342

Gnomad4 OTH AF: 0.000967

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mucopolysaccharidosis type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs150523349; hg19: chr4-996501;