rs10176426

Variant names:

• chr2-233671269-C-T
• rs10176426
• NM_019075.4:c.855+33892C>T

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+33892C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,252 control chromosomes in the GnomAD database, including 543 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 0.070 (543 hom., cov: 33)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 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+33892C>T		intron	N/A	NP_061948.1	Q5DT02
	UGT1A8	NM_019076.5	MANE Select	c.855+52707C>T		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+33892C>T		intron	N/A	ENSP00000343838.5	Q9HAW8-1
	UGT1A8	ENST00000373450.5	TSL:1 MANE Select	c.855+52707C>T		intron	N/A	ENSP00000362549.4	Q9HAW9-1
	UGT1A10	ENST00000373445.1	TSL:1	c.855+33892C>T		intron	N/A	ENSP00000362544.1	Q9HAW8-2

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10689 AN: 152134 Hom.: 542 Cov.: 33

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0852

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

GnomAD4 genome AF: 0.0702 AC: 10694 AN: 152252 Hom.: 543 Cov.: 33 AF XY: 0.0669 AC XY: 4978 AN XY: 74446

African (AFR) AF: 0.0241 AC: 1002 AN: 41550

American (AMR) AF: 0.0646 AC: 988 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0373 AC: 180 AN: 4820

European-Finnish (FIN) AF: 0.0440 AC: 467 AN: 10606

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7366 AN: 68016

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

Alfa AF: 0.0902 Hom.: 841

Bravo AF: 0.0711

Asia WGS AF: 0.0210 AC: 74 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.76
PhyloP100		-1.4
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: rs10176426;

hg19: chr2-234579915;