chr2-233618472-A-G
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
NM_019076.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.81
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]
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 | 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 | c.765A>G | p.Thr255= | synonymous_variant | 1/5 | 1 | NM_019076.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.158 AC: 24061AN: 152080Hom.: 2051 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
24061
AN:
152080
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.128 AC: 32264AN: 251114Hom.: 2436 AF XY: 0.125 AC XY: 17021AN XY: 135712
GnomAD3 exomes
AF:
AC:
32264
AN:
251114
Hom.:
AF XY:
AC XY:
17021
AN XY:
135712
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.148 AC: 215952AN: 1461640Hom.: 16923 Cov.: 35 AF XY: 0.145 AC XY: 105193AN XY: 727130
GnomAD4 exome
AF:
AC:
215952
AN:
1461640
Hom.:
Cov.:
35
AF XY:
AC XY:
105193
AN XY:
727130
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.158 AC: 24092AN: 152198Hom.: 2057 Cov.: 32 AF XY: 0.153 AC XY: 11368AN XY: 74430
GnomAD4 genome
?
AF:
AC:
24092
AN:
152198
Hom.:
Cov.:
32
AF XY:
AC XY:
11368
AN XY:
74430
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
294
AN:
3478
EpiCase
AF:
EpiControl
AF:
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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at