2-233671807-ATT-AT

Variant names:

• chr2-233671807-AT-A
• rs3832043
• NM_019075.4:c.855+34440delT

Variant summary

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

The NM_019075.4(UGT1A10):​c.855+34440delT 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
• Publications: 41 publications found

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]

UGT1A (HGNC:12529):

UGT1A9 (HGNC:12541): (UDP glucuronosyltransferase family 1 member A9) 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 is active on phenols. [provided by RefSeq, Jul 2008]

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019075.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	NM_019075.4	MANE Select	c.855+34440delT		intron	N/A	NP_061948.1	Q5DT02
	UGT1A8	NM_019076.5	MANE Select	c.855+53255delT		intron	N/A	NP_061949.3
	UGT1A9	NM_021027.3	MANE Select	c.-127delT		upstream_gene	N/A	NP_066307.1	O60656-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	ENST00000344644.10	TSL:1 MANE Select	c.855+34431delT		intron	N/A	ENSP00000343838.5	Q9HAW8-1
	UGT1A8	ENST00000373450.5	TSL:1 MANE Select	c.855+53246delT		intron	N/A	ENSP00000362549.4	Q9HAW9-1
	UGT1A10	ENST00000373445.1	TSL:1	c.855+34431delT		intron	N/A	ENSP00000362544.1	Q9HAW8-2

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

African (AFR) AF: 0.563 AC: 15071 AN: 26764

American (AMR) AF: 0.487 AC: 8691 AN: 17838

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 10054 AN: 17236

East Asian (EAS) AF: 0.414 AC: 13309 AN: 32176

South Asian (SAS) AF: 0.636 AC: 31423 AN: 49398

European-Finnish (FIN) AF: 0.685 AC: 27673 AN: 40402

Middle Eastern (MID) AF: 0.591 AC: 2863 AN: 4842

European-Non Finnish (NFE) AF: 0.640 AC: 625586 AN: 978208

Other (OTH) AF: 0.612 AC: 30587 AN: 49976

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

African (AFR) AF: 0.552 AC: 22815 AN: 41302

American (AMR) AF: 0.511 AC: 7766 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1984 AN: 3458

East Asian (EAS) AF: 0.420 AC: 2162 AN: 5142

South Asian (SAS) AF: 0.649 AC: 3099 AN: 4778

European-Finnish (FIN) AF: 0.703 AC: 7381 AN: 10504

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.631 AC: 42803 AN: 67882

Other (OTH) AF: 0.573 AC: 1199 AN: 2092

Alfa AF: 0.506 Hom.: 1434

Bravo AF: 0.572

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3832043;

hg19: chr2-234580453;