rs17864686
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_019077.3(UGT1A7):c.756G>A(p.Leu252Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,613,738 control chromosomes in the GnomAD database, including 37,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.18 ( 2738 hom., cov: 32)
Exomes 𝑓: 0.21 ( 34485 hom. )
Consequence
UGT1A7
NM_019077.3 synonymous
NM_019077.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.54
Genes affected
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]
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]
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
Variant 2-233682693-G-A is Benign according to our data. Variant chr2-233682693-G-A is described in ClinVar as [Benign]. Clinvar id is 440390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.54 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UGT1A7 | NM_019077.3 | c.756G>A | p.Leu252Leu | synonymous_variant | 1/5 | ENST00000373426.4 | NP_061950.2 | |
UGT1A10 | NM_019075.4 | c.855+45316G>A | intron_variant | ENST00000344644.10 | NP_061948.1 | |||
UGT1A8 | NM_019076.5 | c.855+64131G>A | intron_variant | ENST00000373450.5 | NP_061949.3 | |||
UGT1A9 | NM_021027.3 | c.855+9904G>A | intron_variant | ENST00000354728.5 | NP_066307.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UGT1A7 | ENST00000373426.4 | c.756G>A | p.Leu252Leu | synonymous_variant | 1/5 | 1 | NM_019077.3 | ENSP00000362525.3 | ||
UGT1A10 | ENST00000344644.10 | c.855+45316G>A | intron_variant | 1 | NM_019075.4 | ENSP00000343838.5 | ||||
UGT1A9 | ENST00000354728.5 | c.855+9904G>A | intron_variant | 1 | NM_021027.3 | ENSP00000346768.4 | ||||
UGT1A8 | ENST00000373450.5 | c.855+64131G>A | intron_variant | 1 | NM_019076.5 | ENSP00000362549.4 |
Frequencies
GnomAD3 genomes AF: 0.182 AC: 27595AN: 152028Hom.: 2732 Cov.: 32
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GnomAD3 exomes AF: 0.198 AC: 49676AN: 250998Hom.: 5217 AF XY: 0.200 AC XY: 27087AN XY: 135634
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GnomAD4 exome AF: 0.214 AC: 313247AN: 1461592Hom.: 34485 Cov.: 36 AF XY: 0.213 AC XY: 155185AN XY: 727104
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GnomAD4 genome AF: 0.182 AC: 27623AN: 152146Hom.: 2738 Cov.: 32 AF XY: 0.178 AC XY: 13272AN XY: 74376
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 30, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at