rs10028494

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B7	NM_001074.4	c.1003-1956A>C		intron_variant		ENST00000305231.12
UGT2B7	NM_001330719.2	c.1003-1956A>C		intron_variant
UGT2B7	NM_001349568.2	c.256-1956A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B7	ENST00000305231.12	c.1003-1956A>C		intron_variant		1	NM_001074.4	P1

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

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.171

Alfa AF: 0.212 Hom.: 4645

Bravo AF: 0.175

Asia WGS AF: 0.186 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs10028494; hg19: chr4-69970937;