rs17863778

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_019077.3(UGT1A7):c.391C>A(p.Arg131=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.934

Variant links:

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]

UGT1A7 links:

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]

UGT1A10 links:

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]

UGT1A8 links:

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]

UGT1A9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UGT1A7	NM_019077.3 linkuse as main transcript	c.391C>A	p.Arg131=	synonymous_variant	1/5	ENST00000373426.4	NP_061950.2
UGT1A10	NM_019075.4 linkuse as main transcript	c.855+44951C>A		intron_variant		ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5 linkuse as main transcript	c.855+63766C>A		intron_variant		ENST00000373450.5	NP_061949.3
UGT1A9	NM_021027.3 linkuse as main transcript	c.855+9539C>A		intron_variant		ENST00000354728.5	NP_066307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT1A7	ENST00000373426.4 linkuse as main transcript	c.391C>A	p.Arg131=	synonymous_variant	1/5	1	NM_019077.3	ENSP00000362525	P1	Q9HAW7-1
UGT1A10	ENST00000344644.10 linkuse as main transcript	c.855+44951C>A		intron_variant		1	NM_019075.4	ENSP00000343838	P1	Q9HAW8-1
UGT1A9	ENST00000354728.5 linkuse as main transcript	c.855+9539C>A		intron_variant		1	NM_021027.3	ENSP00000346768	P1	O60656-1
UGT1A8	ENST00000373450.5 linkuse as main transcript	c.855+63766C>A		intron_variant		1	NM_019076.5	ENSP00000362549	P1	Q9HAW9-1

Frequencies

GnomAD3 genomes

AF:

0.613

AC:

92575

AN:

151058

Hom.:

28559

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.588

AC:

142405

AN:

242314

Hom.:

42983

AF XY:

0.595

AC XY:

78060

AN XY:

131250

show subpopulations

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 SAS exome

AF:

0.651

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.:

AF XY:

0.624

AC XY:

453380

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.625

Gnomad4 AMR exome

AF:

0.439

Gnomad4 ASJ exome

AF:

0.574

Gnomad4 EAS exome

AF:

0.401

Gnomad4 SAS exome

AF:

0.649

Gnomad4 FIN exome

AF:

0.690

Gnomad4 NFE exome

AF:

0.634

Gnomad4 OTH exome

AF:

0.611

GnomAD4 genome

AF:

0.613

AC:

92651

AN:

151174

Hom.:

28585

Cov.:

AF XY:

0.613

AC XY:

45219

AN XY:

73816

show subpopulations

Gnomad4 AFR

AF:

0.624

Gnomad4 AMR

AF:

0.514

Gnomad4 ASJ

AF:

0.572

Gnomad4 EAS

AF:

0.424

Gnomad4 SAS

AF:

0.652

Gnomad4 FIN

AF:

0.700

Gnomad4 NFE

AF:

0.629

Gnomad4 OTH

AF:

0.587

Alfa

AF:

0.596

Hom.:

7288

Bravo

AF:

0.596

Asia WGS

AF:

0.542

AC:

1886

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.72

CADD

Benign

0.76

DANN

Benign

0.60

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over