2-233687304-G-A

Variant names:

• chr2-233687304-G-A
• rs6736743
• NM_019075.4:c.855+49927G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019075.4(UGT1A10):​c.855+49927G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,878 control chromosomes in the GnomAD database, including 11,933 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 (11933 hom., cov: 31)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 8 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):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019075.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	NM_019075.4	MANE Select	c.855+49927G>A		intron	N/A	NP_061948.1
	UGT1A8	NM_019076.5	MANE Select	c.855+68742G>A		intron	N/A	NP_061949.3
	UGT1A7	NM_019077.3	MANE Select	c.855+4512G>A		intron	N/A	NP_061950.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	ENST00000344644.10	TSL:1 MANE Select	c.855+49927G>A		intron	N/A	ENSP00000343838.5
	UGT1A9	ENST00000354728.5	TSL:1 MANE Select	c.855+14515G>A		intron	N/A	ENSP00000346768.4
	UGT1A7	ENST00000373426.4	TSL:1 MANE Select	c.855+4512G>A		intron	N/A	ENSP00000362525.3

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59706 AN: 151760 Hom.: 11936 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.501

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: 0.402

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.393 AC: 59722 AN: 151878 Hom.: 11933 Cov.: 31 AF XY: 0.398 AC XY: 29537 AN XY: 74210

African (AFR) AF: 0.375 AC: 15530 AN: 41394

American (AMR) AF: 0.338 AC: 5161 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1612 AN: 3466

East Asian (EAS) AF: 0.231 AC: 1192 AN: 5160

South Asian (SAS) AF: 0.455 AC: 2182 AN: 4800

European-Finnish (FIN) AF: 0.517 AC: 5445 AN: 10530

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27250 AN: 67948

Other (OTH) AF: 0.369 AC: 779 AN: 2112

Alfa AF: 0.392 Hom.: 17106

Bravo AF: 0.377

Asia WGS AF: 0.335 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.82
DANN	Benign	0.35
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6736743; hg19: chr2-234595950;