2-233670116-T-C

Variant names:

• chr2-233670116-T-C
• rs13418420
• NM_019075.4:c.855+32739T>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+32739T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,178 control chromosomes in the GnomAD database, including 4,813 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 0.24 (4813 hom., cov: 33)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	NM_019075.4	MANE Select	c.855+32739T>C		intron	N/A	NP_061948.1
	UGT1A8	NM_019076.5	MANE Select	c.855+51554T>C		intron	N/A	NP_061949.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	ENST00000344644.10	TSL:1 MANE Select	c.855+32739T>C		intron	N/A	ENSP00000343838.5
	UGT1A8	ENST00000373450.5	TSL:1 MANE Select	c.855+51554T>C		intron	N/A	ENSP00000362549.4
	UGT1A10	ENST00000373445.1	TSL:1	c.855+32739T>C		intron	N/A	ENSP00000362544.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36794 AN: 152060 Hom.: 4808 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.242 AC: 36824 AN: 152178 Hom.: 4813 Cov.: 33 AF XY: 0.242 AC XY: 17972 AN XY: 74386

African (AFR) AF: 0.195 AC: 8101 AN: 41524

American (AMR) AF: 0.252 AC: 3853 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 880 AN: 3462

East Asian (EAS) AF: 0.526 AC: 2715 AN: 5166

South Asian (SAS) AF: 0.279 AC: 1344 AN: 4820

European-Finnish (FIN) AF: 0.183 AC: 1933 AN: 10584

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17154 AN: 68008

Other (OTH) AF: 0.262 AC: 553 AN: 2112

Alfa AF: 0.238 Hom.: 1209

Bravo AF: 0.246

Asia WGS AF: 0.399 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.55
PhyloP100		0.20
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: rs13418420; hg19: chr2-234578762;