rs7571337

Variant names:

• chr2-233657772-T-C
• rs7571337
• NM_019075.4:c.855+20395T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-233657772-T-C
• chr2-233657772-T-G

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+20395T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,058 control chromosomes in the GnomAD database, including 22,228 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 0.53 (22228 hom., cov: 32)
• Consequence: UGT1A10 NM_019075.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 10 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]

UGT1A (HGNC:12529):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 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+20395T>C		intron	N/A	NP_061948.1
	UGT1A8	NM_019076.5	MANE Select	c.855+39210T>C		intron	N/A	NP_061949.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT1A10	ENST00000344644.10	TSL:1 MANE Select	c.855+20395T>C		intron	N/A	ENSP00000343838.5
	UGT1A8	ENST00000373450.5	TSL:1 MANE Select	c.855+39210T>C		intron	N/A	ENSP00000362549.4
	UGT1A10	ENST00000373445.1	TSL:1	c.855+20395T>C		intron	N/A	ENSP00000362544.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80999 AN: 151940 Hom.: 22184 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.533 AC: 81106 AN: 152058 Hom.: 22228 Cov.: 32 AF XY: 0.523 AC XY: 38898 AN XY: 74338

African (AFR) AF: 0.656 AC: 27217 AN: 41464

American (AMR) AF: 0.514 AC: 7855 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1389 AN: 3470

East Asian (EAS) AF: 0.556 AC: 2878 AN: 5174

South Asian (SAS) AF: 0.395 AC: 1902 AN: 4818

European-Finnish (FIN) AF: 0.392 AC: 4146 AN: 10568

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.502 AC: 34097 AN: 67964

Other (OTH) AF: 0.532 AC: 1124 AN: 2112

Alfa AF: 0.497 Hom.: 39624

Bravo AF: 0.549

Asia WGS AF: 0.509 AC: 1765 AN: 3476

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	0.55
PhyloP100		-1.8
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: rs7571337; hg19: chr2-234566418;