rs17868320

Variant names:

• chr2-233669782-C-T
• rs17868320
• NM_019075.4:c.855+32405C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019075.4(UGT1A10):​c.855+32405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0398 in 152,236 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.040 (143 hom., cov: 32)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.196
• Publications: 44 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-233669782-C-T is Benign according to our data. Variant chr2-233669782-C-T is described in ClinVar as Benign. ClinVar VariationId is 1263192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT1A10	NM_019075.4	c.855+32405C>T		intron_variant	Intron 1 of 4	ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5	c.855+51220C>T		intron_variant	Intron 1 of 4	ENST00000373450.5	NP_061949.3
UGT1A		n.233669782C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT1A10	ENST00000344644.10	c.855+32405C>T		intron_variant	Intron 1 of 4	1	NM_019075.4	ENSP00000343838.5
UGT1A8	ENST00000373450.5	c.855+51220C>T		intron_variant	Intron 1 of 4	1	NM_019076.5	ENSP00000362549.4
UGT1A10	ENST00000373445.1	c.855+32405C>T		intron_variant	Intron 1 of 4	1		ENSP00000362544.1

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 6070 AN: 152118 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0408

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0398 AC: 6066 AN: 152236 Hom.: 143 Cov.: 32 AF XY: 0.0371 AC XY: 2759 AN XY: 74440

African (AFR) AF: 0.0215 AC: 895 AN: 41546

American (AMR) AF: 0.0407 AC: 622 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4824

European-Finnish (FIN) AF: 0.0281 AC: 298 AN: 10606

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0582 AC: 3958 AN: 67998

Other (OTH) AF: 0.0359 AC: 76 AN: 2116

Alfa AF: 0.0273 Hom.: 24

Bravo AF: 0.0403

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 15284532, 19715905) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.68
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: rs17868320; hg19: chr2-234578428;