rs6736508

Variant names:

• chr2-233687101-G-A
• rs6736508
• NM_019075.4:c.855+49724G>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+49724G>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 152,056 control chromosomes in the GnomAD database, including 11,951 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 (11951 hom., cov: 32)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 14 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=-1.06).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	NM_019075.4	MANE Select	c.855+49724G>A		intron	N/A	NP_061948.1	Q5DT02
	UGT1A8	NM_019076.5	MANE Select	c.855+68539G>A		intron	N/A	NP_061949.3
	UGT1A7	NM_019077.3	MANE Select	c.855+4309G>A		intron	N/A	NP_061950.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	ENST00000344644.10	TSL:1 MANE Select	c.855+49724G>A		intron	N/A	ENSP00000343838.5	Q9HAW8-1
	UGT1A9	ENST00000354728.5	TSL:1 MANE Select	c.855+14312G>A		intron	N/A	ENSP00000346768.4	O60656-1
	UGT1A7	ENST00000373426.4	TSL:1 MANE Select	c.855+4309G>A		intron	N/A	ENSP00000362525.3	Q9HAW7-1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59792 AN: 151938 Hom.: 11954 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.393 AC: 59808 AN: 152056 Hom.: 11951 Cov.: 32 AF XY: 0.398 AC XY: 29588 AN XY: 74330

African (AFR) AF: 0.375 AC: 15556 AN: 41454

American (AMR) AF: 0.338 AC: 5165 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1615 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1202 AN: 5188

South Asian (SAS) AF: 0.455 AC: 2193 AN: 4822

European-Finnish (FIN) AF: 0.518 AC: 5466 AN: 10558

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

European-Non Finnish (NFE) AF: 0.401 AC: 27266 AN: 67978

Other (OTH) AF: 0.368 AC: 774 AN: 2104

Alfa AF: 0.392 Hom.: 17692

Bravo AF: 0.376

Asia WGS AF: 0.335 AC: 1170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.43
DANN	Benign	0.72
PhyloP100		-1.6
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: rs6736508; hg19: chr2-234595747;