rs7608175

Variant names:

• chr2-233690443-C-G
• rs7608175
• NM_019075.4:c.855+53066C>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+53066C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,281,456 control chromosomes in the GnomAD database, including 105,680 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 (11700 hom., cov: 32)
  • Exomes 𝑓: 0.41 (93980 hom.)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 19 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=-0.83).
• 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+53066C>G		intron	N/A	NP_061948.1	Q5DT02
	UGT1A8	NM_019076.5	MANE Select	c.855+71881C>G		intron	N/A	NP_061949.3
	UGT1A7	NM_019077.3	MANE Select	c.855+7651C>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+53066C>G		intron	N/A	ENSP00000343838.5	Q9HAW8-1
	UGT1A9	ENST00000354728.5	TSL:1 MANE Select	c.855+17654C>G		intron	N/A	ENSP00000346768.4	O60656-1
	UGT1A7	ENST00000373426.4	TSL:1 MANE Select	c.855+7651C>G		intron	N/A	ENSP00000362525.3	Q9HAW7-1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59139 AN: 151918 Hom.: 11700 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.337

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: 0.367

GnomAD4 exome AF: 0.405 AC: 457739 AN: 1129420 Hom.: 93980 AF XY: 0.408 AC XY: 226255 AN XY: 554534

African (AFR) AF: 0.366 AC: 8849 AN: 24158

American (AMR) AF: 0.268 AC: 7518 AN: 28068

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 7275 AN: 15782

East Asian (EAS) AF: 0.232 AC: 2969 AN: 12798

South Asian (SAS) AF: 0.452 AC: 34226 AN: 75752

European-Finnish (FIN) AF: 0.484 AC: 6297 AN: 13018

Middle Eastern (MID) AF: 0.421 AC: 1845 AN: 4384

European-Non Finnish (NFE) AF: 0.407 AC: 372233 AN: 914212

Other (OTH) AF: 0.401 AC: 16527 AN: 41248

GnomAD4 genome AF: 0.389 AC: 59155 AN: 152036 Hom.: 11700 Cov.: 32 AF XY: 0.394 AC XY: 29277 AN XY: 74294

African (AFR) AF: 0.361 AC: 14961 AN: 41454

American (AMR) AF: 0.336 AC: 5143 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1192 AN: 5164

South Asian (SAS) AF: 0.455 AC: 2183 AN: 4802

European-Finnish (FIN) AF: 0.517 AC: 5470 AN: 10580

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

European-Non Finnish (NFE) AF: 0.401 AC: 27252 AN: 67970

Other (OTH) AF: 0.364 AC: 769 AN: 2112

Alfa AF: 0.392 Hom.: 1623

Bravo AF: 0.372

Asia WGS AF: 0.334 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.43
PhyloP100		0.11
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: rs7608175; hg19: chr2-234599089; COSMIC: COSV59402015; COSMIC: COSV59402015;