rs6431558

Positions:

• chr2-233620997-C-T

Variant summary

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

The NM_019076.5(UGT1A8):​c.855+2435C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,838 control chromosomes in the GnomAD database, including 19,000 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 0.49 (19000 hom., cov: 30)
• Consequence: UGT1A8 NM_019076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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]

UGT1A (HGNC:12529):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT1A8	NM_019076.5	c.855+2435C>T		intron_variant		ENST00000373450.5	NP_061949.3
UGT1A		n.233620997C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT1A8	ENST00000373450.5	c.855+2435C>T		intron_variant		1	NM_019076.5	ENSP00000362549.4

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74989 AN: 151720 Hom.: 18977 Cov.: 30

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.494 AC: 75061 AN: 151838 Hom.: 19000 Cov.: 30 AF XY: 0.484 AC XY: 35909 AN XY: 74204

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.490

Alfa AF: 0.488 Hom.: 2251

Bravo AF: 0.507

Asia WGS AF: 0.502 AC: 1742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6431558; hg19: chr2-234529643;