rs10929303

Variant names:

• chr2-233772770-T-C
• rs10929303
• ENST00000450233.1:n.*612T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-233772770-T-C
• chr2-233772770-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000450233.1(UGT1A4):​n.*612T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 1,348,090 control chromosomes in the GnomAD database, including 415,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42437 hom., cov: 30)
  • Exomes 𝑓: 0.79 (372776 hom.)
• Consequence: UGT1A4 ENST00000450233.1 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.21
• Publications: 60 publications found

Genes affected

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]

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]

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]

UGT1A (HGNC:12529):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-233772770-T-C is Benign according to our data. Variant chr2-233772770-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 335084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT1A4	NM_007120.3	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000373409.8	NP_009051.1
UGT1A5	NM_019078.2	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000373414.4	NP_061951.1
UGT1A3	NM_019093.4	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000482026.6	NP_061966.1
UGT1A1	NM_000463.3	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000305208.10	NP_000454.1
UGT1A6	NM_001072.4	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000305139.11	NP_001063.2
UGT1A10	NM_019075.4	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000373450.5	NP_061949.3
UGT1A7	NM_019077.3	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000373426.4	NP_061950.2
UGT1A9	NM_021027.3	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000354728.5	NP_066307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT1A4	ENST00000373409.8	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_007120.3	ENSP00000362508.4
UGT1A5	ENST00000373414.4	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_019078.2	ENSP00000362513.3
UGT1A3	ENST00000482026.6	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_019093.4	ENSP00000418532.1
UGT1A1	ENST00000305208.10	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_000463.3	ENSP00000304845.5
UGT1A6	ENST00000305139.11	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_001072.4	ENSP00000303174.6
UGT1A10	ENST00000344644.10	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_019075.4	ENSP00000343838.5
UGT1A9	ENST00000354728.5	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_021027.3	ENSP00000346768.4
UGT1A7	ENST00000373426.4	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_019077.3	ENSP00000362525.3
UGT1A8	ENST00000373450.5	c.*211T>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_019076.5	ENSP00000362549.4

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112607 AN: 151584 Hom.: 42404 Cov.: 30

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.788 AC: 943121 AN: 1196390 Hom.: 372776 Cov.: 19 AF XY: 0.789 AC XY: 460234 AN XY: 583332

African (AFR) AF: 0.609 AC: 16091 AN: 26440

American (AMR) AF: 0.746 AC: 14901 AN: 19984

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 12633 AN: 18164

East Asian (EAS) AF: 0.891 AC: 29566 AN: 33194

South Asian (SAS) AF: 0.819 AC: 48577 AN: 59330

European-Finnish (FIN) AF: 0.872 AC: 23854 AN: 27370

Middle Eastern (MID) AF: 0.779 AC: 2620 AN: 3362

European-Non Finnish (NFE) AF: 0.789 AC: 756109 AN: 958552

Other (OTH) AF: 0.775 AC: 38770 AN: 49994

GnomAD4 genome AF: 0.743 AC: 112696 AN: 151700 Hom.: 42437 Cov.: 30 AF XY: 0.750 AC XY: 55543 AN XY: 74078

African (AFR) AF: 0.611 AC: 25233 AN: 41302

American (AMR) AF: 0.754 AC: 11473 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2422 AN: 3466

East Asian (EAS) AF: 0.883 AC: 4565 AN: 5172

South Asian (SAS) AF: 0.822 AC: 3939 AN: 4792

European-Finnish (FIN) AF: 0.888 AC: 9328 AN: 10510

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53286 AN: 67928

Other (OTH) AF: 0.726 AC: 1530 AN: 2108

Alfa AF: 0.769 Hom.: 182222

Bravo AF: 0.726

Asia WGS AF: 0.832 AC: 2894 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Lucey-Driscoll syndrome Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Crigler-Najjar syndrome Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Gilbert syndrome Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.30
PhyloP100		-1.2
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

Other links and lift over

dbSNP: rs10929303; hg19: chr2-234681416;