2-233635253-G-C

Position:

• chr2-233635253-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019076.5(UGT1A8):​c.855+16691G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 149,720 control chromosomes in the GnomAD database, including 43,550 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 0.75 (43550 hom., cov: 29)
• Consequence: UGT1A8 NM_019076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.794

Genes affected

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT1A8	NM_019076.5	c.855+16691G>C		intron_variant		ENST00000373450.5	NP_061949.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT1A8	ENST00000373450.5	c.855+16691G>C		intron_variant		1	NM_019076.5	ENSP00000362549	P1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 112742 AN: 149608 Hom.: 43505 Cov.: 29

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.754 AC: 112835 AN: 149720 Hom.: 43550 Cov.: 29 AF XY: 0.749 AC XY: 54697 AN XY: 73002

Gnomad4 AFR AF: 0.723

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.732

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.749

Alfa AF: 0.697 Hom.: 2193

Bravo AF: 0.745

Asia WGS AF: 0.729 AC: 2524 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs2741032; hg19: chr2-234543899;