rs11692021

Variant names:

• chr2-233682559-T-C
• rs11692021
• NM_019077.3:c.622T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-233682559-T-C
• chr2-233682559-T-G

Variant summary

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

The NM_019077.3(UGT1A7):​c.622T>C​(p.Trp208Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,613,636 control chromosomes in the GnomAD database, including 115,745 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9225 hom., cov: 32)
  • Exomes 𝑓: 0.38 (106520 hom.)
• Consequence: UGT1A7 NM_019077.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.39
• Publications: 91 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.3541193E-4).
• BP6: Variant 2-233682559-T-C is Benign according to our data. Variant chr2-233682559-T-C is described in ClinVar as Benign. ClinVar VariationId is 440389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT1A7	NM_019077.3	c.622T>C	p.Trp208Arg	missense_variant	Exon 1 of 5	ENST00000373426.4	NP_061950.2
UGT1A10	NM_019075.4	c.855+45182T>C		intron_variant	Intron 1 of 4	ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5	c.855+63997T>C		intron_variant	Intron 1 of 4	ENST00000373450.5	NP_061949.3
UGT1A9	NM_021027.3	c.855+9770T>C		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.622T>C	p.Trp208Arg	missense_variant	Exon 1 of 5	1	NM_019077.3	ENSP00000362525.3
UGT1A10	ENST00000344644.10	c.855+45182T>C		intron_variant	Intron 1 of 4	1	NM_019075.4	ENSP00000343838.5
UGT1A9	ENST00000354728.5	c.855+9770T>C		intron_variant	Intron 1 of 4	1	NM_021027.3	ENSP00000346768.4
UGT1A8	ENST00000373450.5	c.855+63997T>C		intron_variant	Intron 1 of 4	1	NM_019076.5	ENSP00000362549.4

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51784 AN: 151876 Hom.: 9233 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.318

GnomAD2 exomes AF: 0.349 AC: 87695 AN: 251062 AF XY: 0.360

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.440

Gnomad EAS exome AF: 0.195

Gnomad FIN exome AF: 0.462

Gnomad NFE exome AF: 0.385

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.378 AC: 551905 AN: 1461642 Hom.: 106520 Cov.: 146 AF XY: 0.380 AC XY: 276479 AN XY: 727124

African (AFR) AF: 0.266 AC: 8900 AN: 33472

American (AMR) AF: 0.207 AC: 9249 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 11523 AN: 26132

East Asian (EAS) AF: 0.220 AC: 8736 AN: 39682

South Asian (SAS) AF: 0.411 AC: 35482 AN: 86250

European-Finnish (FIN) AF: 0.451 AC: 24069 AN: 53420

Middle Eastern (MID) AF: 0.392 AC: 2260 AN: 5762

European-Non Finnish (NFE) AF: 0.386 AC: 429514 AN: 1111830

Other (OTH) AF: 0.367 AC: 22172 AN: 60378

GnomAD4 genome AF: 0.341 AC: 51780 AN: 151994 Hom.: 9225 Cov.: 32 AF XY: 0.344 AC XY: 25559 AN XY: 74282

African (AFR) AF: 0.266 AC: 11020 AN: 41468

American (AMR) AF: 0.271 AC: 4144 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1529 AN: 3472

East Asian (EAS) AF: 0.201 AC: 1037 AN: 5162

South Asian (SAS) AF: 0.412 AC: 1977 AN: 4804

European-Finnish (FIN) AF: 0.475 AC: 5006 AN: 10544

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25861 AN: 67952

Other (OTH) AF: 0.315 AC: 666 AN: 2112

Alfa AF: 0.348 Hom.: 6023

Bravo AF: 0.320

TwinsUK AF: 0.378 AC: 1403

ALSPAC AF: 0.398 AC: 1532

ESP6500AA AF: 0.275 AC: 1211

ESP6500EA AF: 0.387 AC: 3331

ExAC AF: 0.351 AC: 42645

EpiCase AF: 0.392

EpiControl AF: 0.391

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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: 19318555, 11677206, 12122597, 11037804) -

Nov 29, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.015
DANN	Benign	0.52
DEOGEN2	Benign	0.14	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.00035	T
MetaRNN	Benign	0.00044	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.38	N
PhyloP100		-6.4
PROVEAN	Benign	2.7	N
REVEL	Benign	0.10
Sift	Benign	0.15	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.022
MutPred		0.20		Gain of helix (P = 0.0128);
MPC		0.19
ClinPred		0.011	T
GERP RS		-8.3
PromoterAI		0.030	Neutral
Varity_R		0.058
gMVP		0.31
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11692021; hg19: chr2-234591205; COSMIC: COSV60831418;