chr2-233771328-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000360418.4(UGT1A1):​c.*1767C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,958 control chromosomes in the GnomAD database, including 3,662 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 0.18 ( 3661 hom., cov: 31)
Exomes 𝑓: 0.036 ( 1 hom. )

Consequence

UGT1A1
ENST00000360418.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.447

Publications

12 publications found
Variant links:
Genes affected
UGT1A1 (HGNC:12530): (UDP glucuronosyltransferase family 1 member A1) 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 preferred substrate of this enzyme is bilirubin, although it also has moderate activity with simple phenols, flavones, and C18 steroids. Mutations in this gene result in Crigler-Najjar syndromes types I and II and in Gilbert syndrome. [provided by RefSeq, Jul 2008]
UGT1A4 (HGNC:12536): (UDP glucuronosyltransferase family 1 member A4) 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. This enzyme has some glucuronidase activity towards bilirubin, although is is more active on amines, steroids, and sapogenins. [provided by RefSeq, Jul 2008]
UGT1A5 (HGNC:12537): (UDP glucuronosyltransferase family 1 member A5) 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. [provided by RefSeq, Jul 2008]
UGT1A3 (HGNC:12535): (UDP glucuronosyltransferase family 1 member A3) 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. Substrates of this enzyme include estrone, 2-hydroxyestrone, and metabolites of benzo alpha-pyrene. [provided by RefSeq, Jul 2008]
UGT1A6 (HGNC:12538): (UDP glucuronosyltransferase family 1 member A6) 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 is active on phenolic and planar compounds. Alternative splicing in the unique 5' end of this gene results in two transcript variants. [provided by RefSeq, Jul 2008]
UGT1A10 (HGNC:12531): (UDP glucuronosyltransferase family 1 member A10) 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 on mycophenolic acid, coumarins, and quinolines. [provided by RefSeq, Jul 2008]
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]
UGT1A7 (HGNC:12539): (UDP glucuronosyltransferase family 1 member A7) 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 moderate glucuronidase activity with phenols. [provided by RefSeq, Jul 2008]
UGT1A9 (HGNC:12541): (UDP glucuronosyltransferase family 1 member A9) 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 is active on phenols. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UGT1A4NM_007120.3 linkc.1308-934C>G intron_variant Intron 4 of 4 ENST00000373409.8 NP_009051.1 P22310-1
UGT1A5NM_019078.2 linkc.1308-934C>G intron_variant Intron 4 of 4 ENST00000373414.4 NP_061951.1 P35504-1Q5DSZ9
UGT1A3NM_019093.4 linkc.1308-934C>G intron_variant Intron 4 of 4 ENST00000482026.6 NP_061966.1 P35503-1Q5DT01
UGT1A1NM_000463.3 linkc.1305-934C>G intron_variant Intron 4 of 4 ENST00000305208.10 NP_000454.1 P22309-1Q5DT03
UGT1A6NM_001072.4 linkc.1302-934C>G intron_variant Intron 4 of 4 ENST00000305139.11 NP_001063.2 P19224-1Q5DSZ8
UGT1A10NM_019075.4 linkc.1296-934C>G intron_variant Intron 4 of 4 ENST00000344644.10 NP_061948.1 Q9HAW8-1Q5DT02
UGT1A8NM_019076.5 linkc.1296-934C>G intron_variant Intron 4 of 4 ENST00000373450.5 NP_061949.3 Q9HAW9-1Q5DSZ6
UGT1A7NM_019077.3 linkc.1296-934C>G intron_variant Intron 4 of 4 ENST00000373426.4 NP_061950.2 Q9HAW7-1Q5DSZ7
UGT1A9NM_021027.3 linkc.1296-934C>G intron_variant Intron 4 of 4 ENST00000354728.5 NP_066307.1 O60656-1Q5DSZ5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UGT1A4ENST00000373409.8 linkc.1308-934C>G intron_variant Intron 4 of 4 1 NM_007120.3 ENSP00000362508.4 P22310-1
UGT1A5ENST00000373414.4 linkc.1308-934C>G intron_variant Intron 4 of 4 1 NM_019078.2 ENSP00000362513.3 P35504-1
UGT1A3ENST00000482026.6 linkc.1308-934C>G intron_variant Intron 4 of 4 1 NM_019093.4 ENSP00000418532.1 P35503-1
UGT1A1ENST00000305208.10 linkc.1305-934C>G intron_variant Intron 4 of 4 1 NM_000463.3 ENSP00000304845.5 P22309-1
UGT1A6ENST00000305139.11 linkc.1302-934C>G intron_variant Intron 4 of 4 1 NM_001072.4 ENSP00000303174.6 P19224-1
UGT1A10ENST00000344644.10 linkc.1296-934C>G intron_variant Intron 4 of 4 1 NM_019075.4 ENSP00000343838.5 Q9HAW8-1
UGT1A9ENST00000354728.5 linkc.1296-934C>G intron_variant Intron 4 of 4 1 NM_021027.3 ENSP00000346768.4 O60656-1
UGT1A7ENST00000373426.4 linkc.1296-934C>G intron_variant Intron 4 of 4 1 NM_019077.3 ENSP00000362525.3 Q9HAW7-1
UGT1A8ENST00000373450.5 linkc.1296-934C>G intron_variant Intron 4 of 4 1 NM_019076.5 ENSP00000362549.4 Q9HAW9-1

Frequencies

GnomAD3 genomes
AF:
0.182
AC:
27632
AN:
151756
Hom.:
3647
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.371
Gnomad AMI
AF:
0.0418
Gnomad AMR
AF:
0.110
Gnomad ASJ
AF:
0.152
Gnomad EAS
AF:
0.112
Gnomad SAS
AF:
0.165
Gnomad FIN
AF:
0.111
Gnomad MID
AF:
0.123
Gnomad NFE
AF:
0.105
Gnomad OTH
AF:
0.161
GnomAD4 exome
AF:
0.0357
AC:
3
AN:
84
Hom.:
1
Cov.:
0
AF XY:
0.0484
AC XY:
3
AN XY:
62
show subpopulations
African (AFR)
AC:
0
AN:
0
American (AMR)
AF:
0.00
AC:
0
AN:
2
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AF:
0.0909
AC:
2
AN:
22
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.0185
AC:
1
AN:
54
Other (OTH)
AF:
0.00
AC:
0
AN:
6
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.182
AC:
27687
AN:
151874
Hom.:
3661
Cov.:
31
AF XY:
0.179
AC XY:
13262
AN XY:
74202
show subpopulations
African (AFR)
AF:
0.372
AC:
15352
AN:
41310
American (AMR)
AF:
0.110
AC:
1683
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.152
AC:
527
AN:
3470
East Asian (EAS)
AF:
0.112
AC:
580
AN:
5170
South Asian (SAS)
AF:
0.164
AC:
786
AN:
4806
European-Finnish (FIN)
AF:
0.111
AC:
1176
AN:
10554
Middle Eastern (MID)
AF:
0.133
AC:
39
AN:
294
European-Non Finnish (NFE)
AF:
0.105
AC:
7156
AN:
67974
Other (OTH)
AF:
0.166
AC:
350
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1004
2009
3013
4018
5022
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
290
580
870
1160
1450
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0546
Hom.:
61
Bravo
AF:
0.188
Asia WGS
AF:
0.163
AC:
568
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.89
DANN
Benign
0.68
PhyloP100
-0.45
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs11888492; hg19: chr2-234679974; API