2-233691295-C-G

Variant names:

• chr2-233691295-C-G
• rs12623271
• NM_019075.4:c.855+53918C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019075.4(UGT1A10):​c.855+53918C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 985,226 control chromosomes in the GnomAD database, including 81,169 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 0.39 (11966 hom., cov: 32)
  • Exomes 𝑓: 0.41 (69203 hom.)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540
• Publications: 8 publications found

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]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019075.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	NM_019075.4	MANE Select	c.855+53918C>G		intron	N/A	NP_061948.1	Q5DT02
	UGT1A8	NM_019076.5	MANE Select	c.855+72733C>G		intron	N/A	NP_061949.3
	UGT1A7	NM_019077.3	MANE Select	c.855+8503C>G		intron	N/A	NP_061950.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	ENST00000344644.10	TSL:1 MANE Select	c.855+53918C>G		intron	N/A	ENSP00000343838.5	Q9HAW8-1
	UGT1A9	ENST00000354728.5	TSL:1 MANE Select	c.855+18506C>G		intron	N/A	ENSP00000346768.4	O60656-1
	UGT1A7	ENST00000373426.4	TSL:1 MANE Select	c.855+8503C>G		intron	N/A	ENSP00000362525.3	Q9HAW7-1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59812 AN: 151942 Hom.: 11968 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.407 AC: 338958 AN: 833166 Hom.: 69203 Cov.: 39 AF XY: 0.408 AC XY: 156849 AN XY: 384752

African (AFR) AF: 0.383 AC: 6040 AN: 15788

American (AMR) AF: 0.322 AC: 317 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 2382 AN: 5156

East Asian (EAS) AF: 0.223 AC: 811 AN: 3630

South Asian (SAS) AF: 0.460 AC: 7578 AN: 16460

European-Finnish (FIN) AF: 0.522 AC: 144 AN: 276

Middle Eastern (MID) AF: 0.409 AC: 664 AN: 1622

European-Non Finnish (NFE) AF: 0.407 AC: 310123 AN: 761948

Other (OTH) AF: 0.399 AC: 10899 AN: 27302

GnomAD4 genome AF: 0.393 AC: 59829 AN: 152060 Hom.: 11966 Cov.: 32 AF XY: 0.398 AC XY: 29601 AN XY: 74338

African (AFR) AF: 0.376 AC: 15596 AN: 41470

American (AMR) AF: 0.338 AC: 5159 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1189 AN: 5158

South Asian (SAS) AF: 0.455 AC: 2193 AN: 4822

European-Finnish (FIN) AF: 0.517 AC: 5464 AN: 10562

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.401 AC: 27262 AN: 67982

Other (OTH) AF: 0.368 AC: 779 AN: 2114

Alfa AF: 0.295 Hom.: 908

Bravo AF: 0.377

Asia WGS AF: 0.336 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.39
PhyloP100		-0.54
PromoterAI		0.0025	Neutral
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: rs12623271; hg19: chr2-234599941;