4-1005657-C-G

Position:

• chr4-1005657-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047415648.1(IDUA):​c.*1264C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,152 control chromosomes in the GnomAD database, including 2,827 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2827 hom., cov: 33)
• Consequence: IDUA XM_047415648.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IDUA	XM_047415648.1	c.*1264C>G		3_prime_UTR_variant	14/15		XP_047271604.1
IDUA	XM_047415649.1	c.*1264C>G		3_prime_UTR_variant	14/16		XP_047271605.1
IDUA	XM_047415651.1	c.*1264C>G		3_prime_UTR_variant	13/14		XP_047271607.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28117 AN: 152034 Hom.: 2827 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.193

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.185 AC: 28140 AN: 152152 Hom.: 2827 Cov.: 33 AF XY: 0.184 AC XY: 13715 AN XY: 74394

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.192

Alfa AF: 0.0628 Hom.: 74

Bravo AF: 0.184

Asia WGS AF: 0.251 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6827815; hg19: chr4-999445;