2-233671603-T-C

Variant names:

• chr2-233671603-T-C
• rs2741046
• NM_019075.4:c.855+34226T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019075.4(UGT1A10):​c.855+34226T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,178 control chromosomes in the GnomAD database, including 4,573 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 0.22 (4573 hom., cov: 33)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.892
• Publications: 12 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):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 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+34226T>C		intron	N/A	NP_061948.1	Q5DT02
	UGT1A8	NM_019076.5	MANE Select	c.855+53041T>C		intron	N/A	NP_061949.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	ENST00000344644.10	TSL:1 MANE Select	c.855+34226T>C		intron	N/A	ENSP00000343838.5	Q9HAW8-1
	UGT1A8	ENST00000373450.5	TSL:1 MANE Select	c.855+53041T>C		intron	N/A	ENSP00000362549.4	Q9HAW9-1
	UGT1A10	ENST00000373445.1	TSL:1	c.855+34226T>C		intron	N/A	ENSP00000362544.1	Q9HAW8-2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32917 AN: 152060 Hom.: 4576 Cov.: 33

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.216 AC: 32907 AN: 152178 Hom.: 4573 Cov.: 33 AF XY: 0.221 AC XY: 16427 AN XY: 74388

African (AFR) AF: 0.0622 AC: 2587 AN: 41560

American (AMR) AF: 0.183 AC: 2795 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1157 AN: 3470

East Asian (EAS) AF: 0.0268 AC: 139 AN: 5184

South Asian (SAS) AF: 0.327 AC: 1576 AN: 4824

European-Finnish (FIN) AF: 0.364 AC: 3848 AN: 10568

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19917 AN: 67968

Other (OTH) AF: 0.202 AC: 427 AN: 2112

Alfa AF: 0.268 Hom.: 8329

Bravo AF: 0.192

Asia WGS AF: 0.168 AC: 587 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.0
DANN	Benign	0.55
PhyloP100		0.89
PromoterAI		-0.030	Neutral
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

Other links and lift over

dbSNP: rs2741046; hg19: chr2-234580249;