rs4663963

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007120.3(UGT1A4):​c.867+21860T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,614 control chromosomes in the GnomAD database, including 24,567 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 0.54 ( 24566 hom., cov: 32)
Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

UGT1A4
NM_007120.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72
Variant links:
Genes affected
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]
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]
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]
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]
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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.03).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UGT1A6NM_001072.4 linkuse as main transcriptc.862-25487T>G intron_variant ENST00000305139.11
UGT1A4NM_007120.3 linkuse as main transcriptc.867+21860T>G intron_variant ENST00000373409.8
UGT1A10NM_019075.4 linkuse as main transcriptc.856-25487T>G intron_variant ENST00000344644.10
UGT1A8NM_019076.5 linkuse as main transcriptc.856-25487T>G intron_variant ENST00000373450.5
UGT1A7NM_019077.3 linkuse as main transcriptc.856-25487T>G intron_variant ENST00000373426.4
UGT1A5NM_019078.2 linkuse as main transcriptc.868-25487T>G intron_variant ENST00000373414.4
UGT1A3NM_019093.4 linkuse as main transcriptc.867+11554T>G intron_variant ENST00000482026.6
UGT1A9NM_021027.3 linkuse as main transcriptc.856-25487T>G intron_variant ENST00000354728.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UGT1A6ENST00000305139.11 linkuse as main transcriptc.862-25487T>G intron_variant 1 NM_001072.4 P1P19224-1
UGT1A10ENST00000344644.10 linkuse as main transcriptc.856-25487T>G intron_variant 1 NM_019075.4 P1Q9HAW8-1
UGT1A9ENST00000354728.5 linkuse as main transcriptc.856-25487T>G intron_variant 1 NM_021027.3 P1O60656-1
UGT1A4ENST00000373409.8 linkuse as main transcriptc.867+21860T>G intron_variant 1 NM_007120.3 P1P22310-1
UGT1A5ENST00000373414.4 linkuse as main transcriptc.868-25487T>G intron_variant 1 NM_019078.2 P1P35504-1
UGT1A7ENST00000373426.4 linkuse as main transcriptc.856-25487T>G intron_variant 1 NM_019077.3 P1Q9HAW7-1
UGT1A8ENST00000373450.5 linkuse as main transcriptc.856-25487T>G intron_variant 1 NM_019076.5 P1Q9HAW9-1
UGT1A3ENST00000482026.6 linkuse as main transcriptc.867+11554T>G intron_variant 1 NM_019093.4 P1P35503-1
ENST00000509542.1 linkuse as main transcriptn.320T>G non_coding_transcript_exon_variant 3/3

Frequencies

GnomAD3 genomes
AF:
0.544
AC:
82474
AN:
151492
Hom.:
24535
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.787
Gnomad AMI
AF:
0.461
Gnomad AMR
AF:
0.481
Gnomad ASJ
AF:
0.536
Gnomad EAS
AF:
0.328
Gnomad SAS
AF:
0.604
Gnomad FIN
AF:
0.487
Gnomad MID
AF:
0.500
Gnomad NFE
AF:
0.437
Gnomad OTH
AF:
0.510
GnomAD4 exome
AF:
0.500
AC:
2
AN:
4
Hom.:
1
Cov.:
0
AC XY:
0
AN XY:
0
show subpopulations
Gnomad4 NFE exome
AF:
1.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.544
AC:
82546
AN:
151610
Hom.:
24566
Cov.:
32
AF XY:
0.542
AC XY:
40195
AN XY:
74098
show subpopulations
Gnomad4 AFR
AF:
0.787
Gnomad4 AMR
AF:
0.480
Gnomad4 ASJ
AF:
0.536
Gnomad4 EAS
AF:
0.328
Gnomad4 SAS
AF:
0.602
Gnomad4 FIN
AF:
0.487
Gnomad4 NFE
AF:
0.437
Gnomad4 OTH
AF:
0.510
Alfa
AF:
0.463
Hom.:
21732
Bravo
AF:
0.552
Asia WGS
AF:
0.474
AC:
1647
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
0.43
DANN
Benign
0.64

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.

Other links and lift over

dbSNP: rs4663963; hg19: chr2-234650193; API