rs17864686

Variant names:

• chr2-233682693-G-A
• rs17864686
• NM_019077.3:c.756G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-233682693-G-A
• chr2-233682693-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.54
• Publications: 13 publications found

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]

UGT1A (HGNC:12529):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.024).
• BP6: Variant 2-233682693-G-A is Benign according to our data. Variant chr2-233682693-G-A is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
UGT1A7	NM_019077.3	c.756G>A	p.Leu252Leu	synonymous_variant	Exon 1 of 5	ENST00000373426.4	NP_061950.2
UGT1A10	NM_019075.4	c.855+45316G>A		intron_variant	Intron 1 of 4	ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5	c.855+64131G>A		intron_variant	Intron 1 of 4	ENST00000373450.5	NP_061949.3
UGT1A9	NM_021027.3	c.855+9904G>A		intron_variant	Intron 1 of 4	ENST00000354728.5	NP_066307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT1A7	ENST00000373426.4	c.756G>A	p.Leu252Leu	synonymous_variant	Exon 1 of 5	1	NM_019077.3	ENSP00000362525.3
UGT1A10	ENST00000344644.10	c.855+45316G>A		intron_variant	Intron 1 of 4	1	NM_019075.4	ENSP00000343838.5
UGT1A9	ENST00000354728.5	c.855+9904G>A		intron_variant	Intron 1 of 4	1	NM_021027.3	ENSP00000346768.4
UGT1A8	ENST00000373450.5	c.855+64131G>A		intron_variant	Intron 1 of 4	1	NM_019076.5	ENSP00000362549.4

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27595 AN: 152028 Hom.: 2732 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.187

GnomAD2 exomes AF: 0.198 AC: 49676 AN: 250998 AF XY: 0.200

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.207

Gnomad FIN exome AF: 0.193

Gnomad NFE exome AF: 0.227

Gnomad OTH exome AF: 0.192

GnomAD4 exome AF: 0.214 AC: 313247 AN: 1461592 Hom.: 34485 Cov.: 36 AF XY: 0.213 AC XY: 155185 AN XY: 727104

African (AFR) AF: 0.107 AC: 3570 AN: 33470

American (AMR) AF: 0.168 AC: 7506 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2880 AN: 26132

East Asian (EAS) AF: 0.161 AC: 6406 AN: 39666

South Asian (SAS) AF: 0.195 AC: 16818 AN: 86250

European-Finnish (FIN) AF: 0.200 AC: 10671 AN: 53416

Middle Eastern (MID) AF: 0.155 AC: 895 AN: 5760

European-Non Finnish (NFE) AF: 0.227 AC: 252384 AN: 1111808

Other (OTH) AF: 0.201 AC: 12117 AN: 60374

GnomAD4 genome AF: 0.182 AC: 27623 AN: 152146 Hom.: 2738 Cov.: 32 AF XY: 0.178 AC XY: 13272 AN XY: 74376

African (AFR) AF: 0.113 AC: 4694 AN: 41508

American (AMR) AF: 0.165 AC: 2529 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3466

East Asian (EAS) AF: 0.195 AC: 1008 AN: 5172

South Asian (SAS) AF: 0.197 AC: 946 AN: 4814

European-Finnish (FIN) AF: 0.184 AC: 1949 AN: 10588

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15567 AN: 67990

Other (OTH) AF: 0.191 AC: 403 AN: 2112

Alfa AF: 0.192 Hom.: 1994

Bravo AF: 0.174

Asia WGS AF: 0.200 AC: 693 AN: 3478

EpiCase AF: 0.208

EpiControl AF: 0.216

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 28, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.4
DANN	Benign	0.73
PhyloP100		-1.5
PromoterAI		-0.022	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: rs17864686; hg19: chr2-234591339; COSMIC: COSV60831800;