NM_001072.4:c.861+130G>T

Variant names:

• chr2-233693995-G-T
• rs7592281
• NM_001072.4:c.861+130G>T

Variant summary

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

The NM_001072.4(UGT1A6):​c.861+130G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.04 in 1,516,734 control chromosomes in the GnomAD database, including 2,435 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 0.064 (470 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1965 hom.)
• Consequence: UGT1A6 NM_001072.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 4 publications found

Genes affected

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]

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):

ENSG00000224814 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001072.4. 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
	UGT1A6	NM_001072.4	MANE Select	c.861+130G>T		intron	N/A	NP_001063.2
	UGT1A10	NM_019075.4	MANE Select	c.855+56618G>T		intron	N/A	NP_061948.1	Q5DT02
	UGT1A8	NM_019076.5	MANE Select	c.856-73039G>T		intron	N/A	NP_061949.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A6	ENST00000305139.11	TSL:1 MANE Select	c.861+130G>T		intron	N/A	ENSP00000303174.6	P19224-1
	UGT1A10	ENST00000344644.10	TSL:1 MANE Select	c.855+56618G>T		intron	N/A	ENSP00000343838.5	Q9HAW8-1
	UGT1A9	ENST00000354728.5	TSL:1 MANE Select	c.855+21206G>T		intron	N/A	ENSP00000346768.4	O60656-1

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9713 AN: 152060 Hom.: 471 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0701

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.0704

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0276

Gnomad OTH AF: 0.0618

GnomAD4 exome AF: 0.0373 AC: 50954 AN: 1364556 Hom.: 1965 AF XY: 0.0385 AC XY: 26027 AN XY: 676542

African (AFR) AF: 0.114 AC: 3510 AN: 30834

American (AMR) AF: 0.0412 AC: 1519 AN: 36844

Ashkenazi Jewish (ASJ) AF: 0.0695 AC: 1498 AN: 21540

East Asian (EAS) AF: 0.202 AC: 7915 AN: 39232

South Asian (SAS) AF: 0.0729 AC: 5327 AN: 73090

European-Finnish (FIN) AF: 0.0751 AC: 3329 AN: 44316

Middle Eastern (MID) AF: 0.0585 AC: 228 AN: 3896

European-Non Finnish (NFE) AF: 0.0237 AC: 25068 AN: 1058168

Other (OTH) AF: 0.0452 AC: 2560 AN: 56636

GnomAD4 genome AF: 0.0638 AC: 9716 AN: 152178 Hom.: 470 Cov.: 32 AF XY: 0.0666 AC XY: 4958 AN XY: 74390

African (AFR) AF: 0.113 AC: 4674 AN: 41510

American (AMR) AF: 0.0407 AC: 623 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0701 AC: 243 AN: 3468

East Asian (EAS) AF: 0.175 AC: 906 AN: 5176

South Asian (SAS) AF: 0.0700 AC: 337 AN: 4814

European-Finnish (FIN) AF: 0.0824 AC: 871 AN: 10576

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0276 AC: 1876 AN: 68018

Other (OTH) AF: 0.0607 AC: 128 AN: 2110

Alfa AF: 0.0363 Hom.: 62

Bravo AF: 0.0643

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.58
PhyloP100		-0.33
PromoterAI		0.00090	Neutral
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: rs7592281; hg19: chr2-234602641; COSMIC: COSV59396015; COSMIC: COSV59396015;