rs11892031

Positions:

• chr2-233656637-A-C
• chr2-233656637-A-T

Variant summary

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

The NM_019075.4(UGT1A10):​c.855+19260A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,188 control chromosomes in the GnomAD database, including 978 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 0.11 (978 hom., cov: 32)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT1A10	NM_019075.4	c.855+19260A>C		intron_variant		ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5	c.855+38075A>C		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+19260A>C		intron_variant		1	NM_019075.4	ENSP00000343838	P1
UGT1A8	ENST00000373450.5	c.855+38075A>C		intron_variant		1	NM_019076.5	ENSP00000362549	P1
UGT1A10	ENST00000373445.1	c.855+19260A>C		intron_variant		1		ENSP00000362544

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16022 AN: 152070 Hom.: 970 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0669

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.0483

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.106 AC: 16059 AN: 152188 Hom.: 978 Cov.: 32 AF XY: 0.102 AC XY: 7626 AN XY: 74404

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0669

Gnomad4 EAS AF: 0.0268

Gnomad4 SAS AF: 0.0482

Gnomad4 FIN AF: 0.0711

Gnomad4 NFE AF: 0.0818

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0788 Hom.: 1204

Bravo AF: 0.112

Asia WGS AF: 0.0570 AC: 196 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.79
DANN	Benign	0.079

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: rs11892031; hg19: chr2-234565283;