chr2-233681970-C-A

Position:

• chr2-233681970-C-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_019077.3(UGT1A7):​c.33C>A​(p.Pro11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,613,798 control chromosomes in the GnomAD database, including 115,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9197 hom., cov: 32)
  • Exomes 𝑓: 0.38 (106438 hom.)
• Consequence: UGT1A7 NM_019077.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.891

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 2-233681970-C-A is Benign according to our data. Variant chr2-233681970-C-A is described in ClinVar as [Benign]. Clinvar id is 440385.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.891 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT1A7	NM_019077.3	c.33C>A	p.Pro11=	synonymous_variant	1/5	ENST00000373426.4
UGT1A10	NM_019075.4	c.855+44593C>A		intron_variant		ENST00000344644.10
UGT1A8	NM_019076.5	c.855+63408C>A		intron_variant		ENST00000373450.5
UGT1A9	NM_021027.3	c.855+9181C>A		intron_variant		ENST00000354728.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT1A7	ENST00000373426.4	c.33C>A	p.Pro11=	synonymous_variant	1/5	1	NM_019077.3	P1
UGT1A10	ENST00000344644.10	c.855+44593C>A		intron_variant		1	NM_019075.4	P1
UGT1A9	ENST00000354728.5	c.855+9181C>A		intron_variant		1	NM_021027.3	P1
UGT1A8	ENST00000373450.5	c.855+63408C>A		intron_variant		1	NM_019076.5	P1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51669 AN: 151934 Hom.: 9205 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.314

GnomAD3 exomes AF: 0.349 AC: 87507 AN: 250826 Hom.: 16397 AF XY: 0.359 AC XY: 48680 AN XY: 135502

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.201

Gnomad ASJ exome AF: 0.438

Gnomad EAS exome AF: 0.195

Gnomad SAS exome AF: 0.411

Gnomad FIN exome AF: 0.462

Gnomad NFE exome AF: 0.385

Gnomad OTH exome AF: 0.352

GnomAD4 exome AF: 0.377 AC: 551676 AN: 1461746 Hom.: 106438 Cov.: 72 AF XY: 0.380 AC XY: 276363 AN XY: 727162

Gnomad4 AFR exome AF: 0.263

Gnomad4 AMR exome AF: 0.206

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.367

GnomAD4 genome AF: 0.340 AC: 51665 AN: 152052 Hom.: 9197 Cov.: 32 AF XY: 0.343 AC XY: 25530 AN XY: 74332

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.271

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.312

Alfa AF: 0.345 Hom.: 4015

Bravo AF: 0.319

Asia WGS AF: 0.285 AC: 997 AN: 3478

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.53
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs7577677; hg19: chr2-234590616; COSMIC: COSV60839190; COSMIC: COSV60839190;