chr2-233671807-AT-A

Position:

• chr2-233671807-AT-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_019075.4(UGT1A10):​c.855+34440del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.59 (27020 hom., cov: 0)
  • Exomes 𝑓: 0.63 (235022 hom.)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.38

Genes affected

UGT1A10 (HGNC:12531): (UDP glucuronosyltransferase family 1 member A10) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has glucuronidase activity on mycophenolic acid, coumarins, and quinolines. [provided by RefSeq, Jul 2008]

UGT1A8 (HGNC:12540): (UDP glucuronosyltransferase family 1 member A8) This gene encodes a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites. This gene is part of a complex locus that encodes several UDP-glucuronosyltransferases. The locus includes thirteen unique alternate first exons followed by four common exons. Four of the alternate first exons are considered pseudogenes. Each of the remaining nine 5' exons may be spliced to the four common exons, resulting in nine proteins with different N-termini and identical C-termini. Each first exon encodes the substrate binding site, and is regulated by its own promoter. The enzyme encoded by this gene has glucuronidase activity with many substrates including coumarins, phenols, anthraquinones, flavones, and some opioids. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT1A10	NM_019075.4	c.855+34440del		intron_variant		ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5	c.855+53255del		intron_variant		ENST00000373450.5	NP_061949.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT1A10	ENST00000344644.10	c.855+34440del		intron_variant		1	NM_019075.4	ENSP00000343838	P1
UGT1A8	ENST00000373450.5	c.855+53255del		intron_variant		1	NM_019076.5	ENSP00000362549	P1
UGT1A10	ENST00000373445.1	c.855+34440del		intron_variant		1		ENSP00000362544

Frequencies

GnomAD3 genomes AF: 0.594 AC: 89908 AN: 151434 Hom.: 26998 Cov.: 0

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.572

GnomAD4 exome AF: 0.629 AC: 765257 AN: 1216840 Hom.: 235022 Cov.: 0 AF XY: 0.629 AC XY: 368789 AN XY: 586142

Gnomad4 AFR exome AF: 0.563

Gnomad4 AMR exome AF: 0.487

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.414

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.685

Gnomad4 NFE exome AF: 0.640

Gnomad4 OTH exome AF: 0.612

GnomAD4 genome AF: 0.594 AC: 89977 AN: 151554 Hom.: 27020 Cov.: 0 AF XY: 0.595 AC XY: 44032 AN XY: 74052

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.573

Bravo AF: 0.572

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs3832043; hg19: chr2-234580453;