chr2-233682328-C-A

Variant names:

• chr2-233682328-C-A
• rs17863778
• NM_019077.3:c.391C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_019077.3(UGT1A7):​c.391C>A​(p.Arg131Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,612,746 control chromosomes in the GnomAD database, including 314,246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28585 hom., cov: 31)
  • Exomes 𝑓: 0.62 (285661 hom.)
• Consequence: UGT1A7 NM_019077.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.934
• Publications: 24 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 2-233682328-C-A is Benign according to our data. Variant chr2-233682328-C-A is described in ClinVar as Benign. ClinVar VariationId is 440387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.934 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019077.3. 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
	UGT1A7	NM_019077.3	MANE Select	c.391C>A	p.Arg131Arg	synonymous	Exon 1 of 5	NP_061950.2
	UGT1A10	NM_019075.4	MANE Select	c.855+44951C>A		intron	N/A	NP_061948.1	Q5DT02
	UGT1A8	NM_019076.5	MANE Select	c.855+63766C>A		intron	N/A	NP_061949.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A7	ENST00000373426.4	TSL:1 MANE Select	c.391C>A	p.Arg131Arg	synonymous	Exon 1 of 5	ENSP00000362525.3	Q9HAW7-1
	UGT1A10	ENST00000344644.10	TSL:1 MANE Select	c.855+44951C>A		intron	N/A	ENSP00000343838.5	Q9HAW8-1
	UGT1A9	ENST00000354728.5	TSL:1 MANE Select	c.855+9539C>A		intron	N/A	ENSP00000346768.4	O60656-1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 92575 AN: 151058 Hom.: 28559 Cov.: 31

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.586

GnomAD2 exomes AF: 0.588 AC: 142405 AN: 242314 AF XY: 0.595

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.421

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.423

Gnomad FIN exome AF: 0.691

Gnomad NFE exome AF: 0.626

Gnomad OTH exome AF: 0.580

GnomAD4 exome AF: 0.622 AC: 909739 AN: 1461572 Hom.: 285661 Cov.: 99 AF XY: 0.624 AC XY: 453380 AN XY: 727072

African (AFR) AF: 0.625 AC: 20932 AN: 33472

American (AMR) AF: 0.439 AC: 19600 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 15002 AN: 26128

East Asian (EAS) AF: 0.401 AC: 15909 AN: 39678

South Asian (SAS) AF: 0.649 AC: 55969 AN: 86248

European-Finnish (FIN) AF: 0.690 AC: 36839 AN: 53400

Middle Eastern (MID) AF: 0.587 AC: 3384 AN: 5764

European-Non Finnish (NFE) AF: 0.634 AC: 705211 AN: 1111836

Other (OTH) AF: 0.611 AC: 36893 AN: 60376

GnomAD4 genome AF: 0.613 AC: 92651 AN: 151174 Hom.: 28585 Cov.: 31 AF XY: 0.613 AC XY: 45219 AN XY: 73816

African (AFR) AF: 0.624 AC: 25721 AN: 41216

American (AMR) AF: 0.514 AC: 7812 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1981 AN: 3462

East Asian (EAS) AF: 0.424 AC: 2170 AN: 5122

South Asian (SAS) AF: 0.652 AC: 3132 AN: 4800

European-Finnish (FIN) AF: 0.700 AC: 7329 AN: 10476

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42523 AN: 67606

Other (OTH) AF: 0.587 AC: 1232 AN: 2100

Alfa AF: 0.596 Hom.: 7288

Bravo AF: 0.596

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.76
DANN	Benign	0.60
PhyloP100		-0.93
PromoterAI		-0.0068	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17863778; hg19: chr2-234590974; COSMIC: COSV60836048; COSMIC: COSV60836048;