Variant chr2-233618537-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_019076.5(UGT1A8):c.830G>A(p.Cys277Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0211 in 1,613,720 control chromosomes in the GnomAD database, including 504 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.013 ( 22 hom., cov: 32)

Exomes 𝑓: 0.022 ( 482 hom. )

Consequence

UGT1A8
NM_019076.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.37

Variant links:

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]

UGT1A8 links:

UGT1A (HGNC:):

UGT1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071814954).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0132 (2010/152216) while in subpopulation NFE AF= 0.0219 (1486/68008). AF 95% confidence interval is 0.0209. There are 22 homozygotes in gnomad4. There are 873 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT1A8	NM_019076.5 linkuse as main transcript	c.830G>A	p.Cys277Tyr	missense_variant	1/5	ENST00000373450.5	NP_061949.3	Q9HAW9-1Q5DSZ6
UGT1A	use as main transcript	n.233618537G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT1A8	ENST00000373450.5 linkuse as main transcript	c.830G>A	p.Cys277Tyr	missense_variant	1/5	1	NM_019076.5	ENSP00000362549.4		Q9HAW9-1

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2012

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00601

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00397

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0219

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0123

AC:

3092

AN:

250656

Hom.:

AF XY:

0.0120

AC XY:

1622

AN XY:

135498

show subpopulations

Gnomad AFR exome

AF:

0.00527

Gnomad AMR exome

AF:

0.00827

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.00444

Gnomad NFE exome

AF:

0.0221

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.0219

AC:

32074

AN:

1461504

Hom.:

482

Cov.:

AF XY:

0.0210

AC XY:

15289

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.00403

Gnomad4 AMR exome

AF:

0.00962

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.00457

Gnomad4 NFE exome

AF:

0.0270

Gnomad4 OTH exome

AF:

0.0177

GnomAD4 genome

AF:

0.0132

AC:

2010

AN:

152216

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

873

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00600

Gnomad4 AMR

AF:

0.0118

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.00397

Gnomad4 NFE

AF:

0.0219

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0146

Hom.:

Bravo

AF:

0.0142

TwinsUK

AF:

0.0278

AC:

103

ALSPAC

AF:

0.0267

AC:

103

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.0222

AC:

191

ExAC

AF:

0.0123

AC:

1488

EpiCase

AF:

0.0203

EpiControl

AF:

0.0229

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0072

MetaSVM

Uncertain

0.24

MutationAssessor

Pathogenic

3.7

PROVEAN

Pathogenic

-10

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.33

ClinPred

0.077

GERP RS

4.0

Varity_R

0.91

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over