rs45549435

Variant names:

• chr2-233691689-CAGGAG-C
• rs45549435
• NM_019075.4:c.855+54318_855+54322delAGGAG

Your query was ambiguous. Multiple possible variants found:

• chr2-233691689-CAGGAG-C
• chr2-233691689-CAGGAG-CAGGAGAGGAG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_019075.4(UGT1A10):​c.855+54318_855+54322delAGGAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 968,978 control chromosomes in the GnomAD database, including 78,686 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (11802 hom., cov: 0)
  • Exomes 𝑓: 0.40 (66884 hom.)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 2 publications found

Genes affected

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]

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]

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):

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT1A10	NM_019075.4	c.855+54318_855+54322delAGGAG		intron_variant	Intron 1 of 4	ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5	c.855+73133_855+73137delAGGAG		intron_variant	Intron 1 of 4	ENST00000373450.5	NP_061949.3
UGT1A7	NM_019077.3	c.855+8903_855+8907delAGGAG		intron_variant	Intron 1 of 4	ENST00000373426.4	NP_061950.2
UGT1A9	NM_021027.3	c.855+18906_855+18910delAGGAG		intron_variant	Intron 1 of 4	ENST00000354728.5	NP_066307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT1A10	ENST00000344644.10	c.855+54318_855+54322delAGGAG		intron_variant	Intron 1 of 4	1	NM_019075.4	ENSP00000343838.5
UGT1A9	ENST00000354728.5	c.855+18906_855+18910delAGGAG		intron_variant	Intron 1 of 4	1	NM_021027.3	ENSP00000346768.4
UGT1A7	ENST00000373426.4	c.855+8903_855+8907delAGGAG		intron_variant	Intron 1 of 4	1	NM_019077.3	ENSP00000362525.3
UGT1A8	ENST00000373450.5	c.855+73133_855+73137delAGGAG		intron_variant	Intron 1 of 4	1	NM_019076.5	ENSP00000362549.4

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59454 AN: 151554 Hom.: 11803 Cov.: 0

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.403 AC: 329124 AN: 817304 Hom.: 66884 AF XY: 0.404 AC XY: 152501 AN XY: 377804

African (AFR) AF: 0.378 AC: 5850 AN: 15480

American (AMR) AF: 0.322 AC: 313 AN: 972

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 2332 AN: 5074

East Asian (EAS) AF: 0.222 AC: 814 AN: 3672

South Asian (SAS) AF: 0.456 AC: 7342 AN: 16108

European-Finnish (FIN) AF: 0.529 AC: 144 AN: 272

Middle Eastern (MID) AF: 0.407 AC: 653 AN: 1606

European-Non Finnish (NFE) AF: 0.403 AC: 301141 AN: 747402

Other (OTH) AF: 0.394 AC: 10535 AN: 26718

GnomAD4 genome AF: 0.392 AC: 59473 AN: 151674 Hom.: 11802 Cov.: 0 AF XY: 0.396 AC XY: 29369 AN XY: 74090

African (AFR) AF: 0.375 AC: 15505 AN: 41370

American (AMR) AF: 0.337 AC: 5135 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1606 AN: 3464

East Asian (EAS) AF: 0.230 AC: 1186 AN: 5156

South Asian (SAS) AF: 0.453 AC: 2179 AN: 4806

European-Finnish (FIN) AF: 0.514 AC: 5397 AN: 10498

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.400 AC: 27129 AN: 67828

Other (OTH) AF: 0.368 AC: 777 AN: 2110

Alfa AF: 0.394 Hom.: 1461

Bravo AF: 0.377

Asia WGS AF: 0.336 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.026
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs45549435; hg19: chr2-234600335;