rs12647681

Positions:

• chr4-69097442-A-C
• chr4-69097442-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.721+201A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,388 control chromosomes in the GnomAD database, including 26,056 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

• Frequency: Genomes: 𝑓 0.58 (26056 hom., cov: 31)
• Consequence: UGT2B7 NM_001074.4 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.0170

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B7	NM_001074.4	c.721+201A>C		intron_variant		ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2	c.721+201A>C		intron_variant			NP_001317648.1
UGT2B7	NM_001349568.2	c.-26-1098A>C		intron_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12	c.721+201A>C		intron_variant		1	NM_001074.4	ENSP00000304811	P1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87067 AN: 151266 Hom.: 26008 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.571

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.576 AC: 87172 AN: 151388 Hom.: 26056 Cov.: 31 AF XY: 0.584 AC XY: 43201 AN XY: 73914

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.588

Alfa AF: 0.516 Hom.: 2628

Bravo AF: 0.590

Asia WGS AF: 0.656 AC: 2279 AN: 3476

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tramadol response Other:1

drug response, no assertion criteria provided

research

Bruce Budowle Laboratory, University of North Texas Health Science Center

Apr 28, 2018

- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.39

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: rs12647681; hg19: chr4-69963160;