rs10028494

Variant names:

• chr4-69105219-A-C
• rs10028494
• NM_001074.4:c.1003-1956A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-69105219-A-C
• chr4-69105219-A-T

Variant summary

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

The NM_001074.4(UGT2B7):​c.1003-1956A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,032 control chromosomes in the GnomAD database, including 2,553 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 0.18 (2553 hom., cov: 31)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 19 publications found

Genes affected

UGT2B7 (HGNC:12554): (UDP glucuronosyltransferase family 2 member B7) The protein encoded by this gene belongs to the UDP-glycosyltransferase (UGT) family. UGTs serve a major role in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This protein is localized in the microsome membrane, and has unique specificity for 3,4-catechol estrogens and estriol, suggesting that it may play an important role in regulating the level and activity of these potent estrogen metabolites. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2017]

ENSG00000299782 (HGNC:58802):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001074.4. 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
	UGT2B7	NM_001074.4	MANE Select	c.1003-1956A>C		intron	N/A	NP_001065.2
	UGT2B7	NM_001330719.2		c.1003-1956A>C		intron	N/A	NP_001317648.1
	UGT2B7	NM_001349568.2		c.256-1956A>C		intron	N/A	NP_001336497.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B7	ENST00000305231.12	TSL:1 MANE Select	c.1003-1956A>C		intron	N/A	ENSP00000304811.7
	UGT2B7	ENST00000508661.5	TSL:2	c.1003-1956A>C		intron	N/A	ENSP00000427659.1
	UGT2B7	ENST00000622664.1	TSL:5	c.1002+2281A>C		intron	N/A	ENSP00000483172.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26900 AN: 151912 Hom.: 2551 Cov.: 31

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.177 AC: 26911 AN: 152032 Hom.: 2553 Cov.: 31 AF XY: 0.173 AC XY: 12847 AN XY: 74308

African (AFR) AF: 0.116 AC: 4806 AN: 41512

American (AMR) AF: 0.152 AC: 2321 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 563 AN: 3466

East Asian (EAS) AF: 0.223 AC: 1146 AN: 5150

South Asian (SAS) AF: 0.157 AC: 758 AN: 4814

European-Finnish (FIN) AF: 0.157 AC: 1660 AN: 10572

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15063 AN: 67954

Other (OTH) AF: 0.171 AC: 360 AN: 2108

Alfa AF: 0.204 Hom.: 6385

Bravo AF: 0.175

Asia WGS AF: 0.186 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.53
PhyloP100		-0.67
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: rs10028494; hg19: chr4-69970937;