2-233691689-CAGGAG-C

Position:

• chr2-233691689-CAGGAG-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_019075.4(UGT1A10):​c.855+54318_855+54322del 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

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]

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
UGT1A10	NM_019075.4	c.855+54318_855+54322del		intron_variant		ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5	c.855+73133_855+73137del		intron_variant		ENST00000373450.5	NP_061949.3
UGT1A7	NM_019077.3	c.855+8903_855+8907del		intron_variant		ENST00000373426.4	NP_061950.2
UGT1A9	NM_021027.3	c.855+18906_855+18910del		intron_variant		ENST00000354728.5	NP_066307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT1A10	ENST00000344644.10	c.855+54318_855+54322del		intron_variant		1	NM_019075.4	ENSP00000343838	P1
UGT1A9	ENST00000354728.5	c.855+18906_855+18910del		intron_variant		1	NM_021027.3	ENSP00000346768	P1
UGT1A7	ENST00000373426.4	c.855+8903_855+8907del		intron_variant		1	NM_019077.3	ENSP00000362525	P1
UGT1A8	ENST00000373450.5	c.855+73133_855+73137del		intron_variant		1	NM_019076.5	ENSP00000362549	P1

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

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.403

Gnomad4 OTH exome AF: 0.394

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

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.400

Gnomad4 OTH AF: 0.368

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs45549435; hg19: chr2-234600335;