2-233681881-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_019075.4(UGT1A10):c.855+44504T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,551,906 control chromosomes in the GnomAD database, including 111,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.34 ( 9238 hom., cov: 33)

Exomes 𝑓: 0.38 ( 102541 hom. )

Consequence

UGT1A10
NM_019075.4 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -3.21

Variant links:

Genes affected

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]

UGT1A10 links:

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]

UGT1A8 links:

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]

UGT1A9 links:

UGT1A (HGNC:12529):

UGT1A links:

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]

UGT1A7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-233681881-T-G is Benign according to our data. Variant chr2-233681881-T-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 440384.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
UGT1A10	NM_019075.4 link	c.855+44504T>G	intron_variant	Intron 1 of 4	ENST00000344644.10	NP_061948.1	Q9HAW8-1Q5DT02
UGT1A8	NM_019076.5 link	c.855+63319T>G	intron_variant	Intron 1 of 4	ENST00000373450.5	NP_061949.3	Q9HAW9-1Q5DSZ6
UGT1A9	NM_021027.3 link	c.855+9092T>G	intron_variant	Intron 1 of 4	ENST00000354728.5	NP_066307.1	O60656-1Q5DSZ5
UGT1A7	NM_019077.3 link	c.-57T>G	upstream_gene_variant		ENST00000373426.4	NP_061950.2	Q9HAW7-1Q5DSZ7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
UGT1A10	ENST00000344644.10 link	c.855+44504T>G	intron_variant	Intron 1 of 4	1	NM_019075.4	ENSP00000343838.5	Q9HAW8-1
UGT1A9	ENST00000354728.5 link	c.855+9092T>G	intron_variant	Intron 1 of 4	1	NM_021027.3	ENSP00000346768.4	O60656-1
UGT1A8	ENST00000373450.5 link	c.855+63319T>G	intron_variant	Intron 1 of 4	1	NM_019076.5	ENSP00000362549.4	Q9HAW9-1
UGT1A7	ENST00000373426.4 link	c.-57T>G	upstream_gene_variant		1	NM_019077.3	ENSP00000362525.3	Q9HAW7-1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51829

AN:

151996

Hom.:

9245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.475

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.317

GnomAD4 exome

AF:

0.379

AC:

530386

AN:

1399792

Hom.:

102541

Cov.:

AF XY:

0.381

AC XY:

263151

AN XY:

690268

show subpopulations

Gnomad4 AFR exome

AF:

0.268

Gnomad4 AMR exome

AF:

0.215

Gnomad4 ASJ exome

AF:

0.439

Gnomad4 EAS exome

AF:

0.220

Gnomad4 SAS exome

AF:

0.415

Gnomad4 FIN exome

AF:

0.451

Gnomad4 NFE exome

AF:

0.386

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.341

AC:

51827

AN:

152114

Hom.:

9238

Cov.:

AF XY:

0.344

AC XY:

25606

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.266

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.439

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.412

Gnomad4 FIN

AF:

0.474

Gnomad4 NFE

AF:

0.381

Gnomad4 OTH

AF:

0.315

Alfa

AF:

0.351

Hom.:

7022

Bravo

AF:

0.320

Asia WGS

AF:

0.287

AC:

1004

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Sep 13, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26202972, 15716465) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.083

DANN

Benign

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over