rs45535938

Positions:

chr2-233693109-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001072.4(UGT1A6):c.105C>T(p.Asp35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,614,076 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 62 hom. )

Consequence

UGT1A6
NM_001072.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.246

Variant links:

Genes affected

UGT1A6 (HGNC:12538): (UDP glucuronosyltransferase family 1 member A6) 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 phenolic and planar compounds. Alternative splicing in the unique 5' end of this gene results in two transcript variants. [provided by RefSeq, Jul 2008]

UGT1A6 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:

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:

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 2-233693109-C-T is Benign according to our data. Variant chr2-233693109-C-T is described in ClinVar as [Benign]. Clinvar id is 810915.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.246 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UGT1A6	NM_001072.4 linkuse as main transcript	c.105C>T	p.Asp35=	synonymous_variant	1/5	ENST00000305139.11
UGT1A10	NM_019075.4 linkuse as main transcript	c.855+55732C>T		intron_variant		ENST00000344644.10
UGT1A8	NM_019076.5 linkuse as main transcript	c.856-73925C>T		intron_variant		ENST00000373450.5
UGT1A7	NM_019077.3 linkuse as main transcript	c.855+10317C>T		intron_variant		ENST00000373426.4
UGT1A9	NM_021027.3 linkuse as main transcript	c.855+20320C>T		intron_variant		ENST00000354728.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT1A6	ENST00000305139.11 linkuse as main transcript	c.105C>T	p.Asp35=	synonymous_variant	1/5	1	NM_001072.4	P1	P19224-1
UGT1A10	ENST00000344644.10 linkuse as main transcript	c.855+55732C>T		intron_variant		1	NM_019075.4	P1	Q9HAW8-1
UGT1A9	ENST00000354728.5 linkuse as main transcript	c.855+20320C>T		intron_variant		1	NM_021027.3	P1	O60656-1
UGT1A7	ENST00000373426.4 linkuse as main transcript	c.855+10317C>T		intron_variant		1	NM_019077.3	P1	Q9HAW7-1
UGT1A8	ENST00000373450.5 linkuse as main transcript	c.856-73925C>T		intron_variant		1	NM_019076.5	P1	Q9HAW9-1

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

387

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0559

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00467

AC:

1173

AN:

251256

Hom.:

AF XY:

0.00426

AC XY:

578

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.0539

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.000379

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00189

AC:

2760

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

1390

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00295

Gnomad4 EAS exome

AF:

0.0493

Gnomad4 SAS exome

AF:

0.00235

Gnomad4 FIN exome

AF:

0.000618

Gnomad4 NFE exome

AF:

0.000185

Gnomad4 OTH exome

AF:

0.00429

GnomAD4 genome

AF:

0.00253

AC:

385

AN:

152232

Hom.:

Cov.:

AF XY:

0.00277

AC XY:

206

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.0556

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000832

Hom.:

Bravo

AF:

0.00247

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Mar 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.1

DANN

Benign

0.80

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

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