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2-233693109-C-T

Variant summary

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

The NM_001072.4(UGT1A6):c.105C>T(p.Asp35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,614,076 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 62 hom. )

Consequence

UGT1A6
NM_001072.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.246
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]
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 made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-233693109-C-T is Benign according to our data. Variant chr2-233693109-C-T is described in ClinVar as [Benign]. Clinvar id is 810915.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.246 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UGT1A6NM_001072.4 linkuse as main transcriptc.105C>T p.Asp35= synonymous_variant 1/5 ENST00000305139.11
UGT1A10NM_019075.4 linkuse as main transcriptc.855+55732C>T intron_variant ENST00000344644.10
UGT1A8NM_019076.5 linkuse as main transcriptc.856-73925C>T intron_variant ENST00000373450.5
UGT1A7NM_019077.3 linkuse as main transcriptc.855+10317C>T intron_variant ENST00000373426.4
UGT1A9NM_021027.3 linkuse as main transcriptc.855+20320C>T intron_variant ENST00000354728.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UGT1A6ENST00000305139.11 linkuse as main transcriptc.105C>T p.Asp35= synonymous_variant 1/51 NM_001072.4 P1P19224-1
UGT1A10ENST00000344644.10 linkuse as main transcriptc.855+55732C>T intron_variant 1 NM_019075.4 P1Q9HAW8-1
UGT1A9ENST00000354728.5 linkuse as main transcriptc.855+20320C>T intron_variant 1 NM_021027.3 P1O60656-1
UGT1A7ENST00000373426.4 linkuse as main transcriptc.855+10317C>T intron_variant 1 NM_019077.3 P1Q9HAW7-1
UGT1A8ENST00000373450.5 linkuse as main transcriptc.856-73925C>T intron_variant 1 NM_019076.5 P1Q9HAW9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00254
AC:
387
AN:
152114
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000893
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.0559
Gnomad SAS
AF:
0.00394
Gnomad FIN
AF:
0.000660
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.00467
AC:
1173
AN:
251256
Hom.:
34
AF XY:
0.00426
AC XY:
578
AN XY:
135788
show subpopulations
Gnomad AFR exome
AF:
0.000615
Gnomad AMR exome
AF:
0.000231
Gnomad ASJ exome
AF:
0.00228
Gnomad EAS exome
AF:
0.0539
Gnomad SAS exome
AF:
0.00235
Gnomad FIN exome
AF:
0.000693
Gnomad NFE exome
AF:
0.000379
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00189
AC:
2760
AN:
1461844
Hom.:
62
Cov.:
84
AF XY:
0.00191
AC XY:
1390
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00295
Gnomad4 EAS exome
AF:
0.0493
Gnomad4 SAS exome
AF:
0.00235
Gnomad4 FIN exome
AF:
0.000618
Gnomad4 NFE exome
AF:
0.000185
Gnomad4 OTH exome
AF:
0.00429
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00253
AC:
385
AN:
152232
Hom.:
9
Cov.:
32
AF XY:
0.00277
AC XY:
206
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.000891
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.0556
Gnomad4 SAS
AF:
0.00395
Gnomad4 FIN
AF:
0.000660
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000832
Hom.:
0
Bravo
AF:
0.00247
Asia WGS
AF:
0.0250
AC:
87
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesMar 23, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
9.1
Dann
Benign
0.80

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: rs45535938; hg19: chr2-234601755; COSMIC: COSV59382154; COSMIC: COSV59382154; API