Variant 2-233618472-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_019076.5(UGT1A8):c.765A>G(p.Thr255=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,838 control chromosomes in the GnomAD database, including 18,980 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2057 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16923 hom. )

Consequence

UGT1A8
NM_019076.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.81

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 2-233618472-A-G is Benign according to our data. Variant chr2-233618472-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 773665.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT1A8	NM_019076.5 linkuse as main transcript	c.765A>G	p.Thr255=	synonymous_variant	1/5	ENST00000373450.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT1A8	ENST00000373450.5 linkuse as main transcript	c.765A>G	p.Thr255=	synonymous_variant	1/5	1	NM_019076.5	P1	Q9HAW9-1

Frequencies

GnomAD3 genomes

AF:

0.158

AC:

24061

AN:

152080

Hom.:

2051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.0921

Gnomad ASJ

AF:

0.0694

Gnomad EAS

AF:

0.0993

Gnomad SAS

AF:

0.0629

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.128

AC:

32264

AN:

251114

Hom.:

2436

AF XY:

0.125

AC XY:

17021

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.0663

Gnomad ASJ exome

AF:

0.0750

Gnomad EAS exome

AF:

0.107

Gnomad SAS exome

AF:

0.0680

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.159

Gnomad OTH exome

AF:

0.125

GnomAD4 exome

AF:

0.148

AC:

215952

AN:

1461640

Hom.:

16923

Cov.:

AF XY:

0.145

AC XY:

105193

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.0712

Gnomad4 ASJ exome

AF:

0.0746

Gnomad4 EAS exome

AF:

0.0664

Gnomad4 SAS exome

AF:

0.0653

Gnomad4 FIN exome

AF:

0.133

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.158

AC:

24092

AN:

152198

Hom.:

2057

Cov.:

AF XY:

0.153

AC XY:

11368

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.0918

Gnomad4 ASJ

AF:

0.0694

Gnomad4 EAS

AF:

0.0990

Gnomad4 SAS

AF:

0.0630

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.162

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.137

Hom.:

711

Bravo

AF:

0.159

Asia WGS

AF:

0.0850

AC:

294

AN:

3478

EpiCase

AF:

0.142

EpiControl

AF:

0.152

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

Cadd

Benign

0.052

Dann

Benign

0.32

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over