4-69096360-T-C

Position:

• chr4-69096360-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349568.2(UGT2B7):​c.-26-2180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,130,256 control chromosomes in the GnomAD database, including 149,632 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 (26313 hom., cov: 32)
  • Exomes 𝑓: 0.49 (123319 hom.)
• Consequence: UGT2B7 NM_001349568.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -1.67

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B7	NM_001349568.2	c.-26-2180T>C		intron_variant			NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000502942.5	c.-26-2180T>C		intron_variant		2		ENSP00000426206
UGT2B7	ENST00000509763.1	n.260-2180T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87599 AN: 151876 Hom.: 26267 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.494 AC: 483291 AN: 978262 Hom.: 123319 AF XY: 0.496 AC XY: 243703 AN XY: 491698

Gnomad4 AFR exome AF: 0.714

Gnomad4 AMR exome AF: 0.683

Gnomad4 ASJ exome AF: 0.510

Gnomad4 EAS exome AF: 0.704

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.578

Gnomad4 NFE exome AF: 0.460

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.577 AC: 87700 AN: 151994 Hom.: 26313 Cov.: 32 AF XY: 0.586 AC XY: 43528 AN XY: 74296

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.588

Alfa AF: 0.506 Hom.: 20999

Bravo AF: 0.590

Asia WGS AF: 0.657 AC: 2283 AN: 3478

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	-0.88
CADD	Benign	0.11
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7668258; hg19: chr4-69962078; COSMIC: COSV59441822;