2-233691295-C-G

Position:

• chr2-233691295-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019075.4(UGT1A10):​c.855+53918C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 985,226 control chromosomes in the GnomAD database, including 81,169 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (11966 hom., cov: 32)
  • Exomes 𝑓: 0.41 (69203 hom.)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT1A10	NM_019075.4	c.855+53918C>G		intron_variant		ENST00000344644.10	NP_061948.1
UGT1A8	NM_019076.5	c.855+72733C>G		intron_variant		ENST00000373450.5	NP_061949.3
UGT1A7	NM_019077.3	c.855+8503C>G		intron_variant		ENST00000373426.4	NP_061950.2
UGT1A9	NM_021027.3	c.855+18506C>G		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+53918C>G		intron_variant		1	NM_019075.4	ENSP00000343838.5
UGT1A9	ENST00000354728.5	c.855+18506C>G		intron_variant		1	NM_021027.3	ENSP00000346768.4
UGT1A7	ENST00000373426.4	c.855+8503C>G		intron_variant		1	NM_019077.3	ENSP00000362525.3
UGT1A8	ENST00000373450.5	c.855+72733C>G		intron_variant		1	NM_019076.5	ENSP00000362549.4

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59812 AN: 151942 Hom.: 11968 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.407 AC: 338958 AN: 833166 Hom.: 69203 Cov.: 39 AF XY: 0.408 AC XY: 156849 AN XY: 384752

Gnomad4 AFR exome AF: 0.383

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.223

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.407

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.393 AC: 59829 AN: 152060 Hom.: 11966 Cov.: 32 AF XY: 0.398 AC XY: 29601 AN XY: 74338

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.368

Alfa AF: 0.295 Hom.: 908

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
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.39

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

Other links and lift over

dbSNP: rs12623271; hg19: chr2-234599941;