4-69096383-G-A

Position:

• chr4-69096383-G-A

Variant summary

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

The NM_001349568.2(UGT2B7):​c.-26-2157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 1,366,818 control chromosomes in the GnomAD database, including 758 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 0.033 (119 hom., cov: 33)
  • Exomes 𝑓: 0.026 (639 hom.)
• Consequence: UGT2B7 NM_001349568.2 intron
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -1.38

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=-0.86).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0996 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B7	NM_001349568.2	c.-26-2157G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B7	ENST00000502942.5	c.-26-2157G>A		intron_variant		2
UGT2B7	ENST00000509763.1	n.260-2157G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5084 AN: 152108 Hom.: 119 Cov.: 33

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0469

GnomAD4 exome AF: 0.0259 AC: 31410 AN: 1214592 Hom.: 639 AF XY: 0.0257 AC XY: 15558 AN XY: 605058

Gnomad4 AFR exome AF: 0.0487

Gnomad4 AMR exome AF: 0.0238

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.0000537

Gnomad4 SAS exome AF: 0.0102

Gnomad4 FIN exome AF: 0.0283

Gnomad4 NFE exome AF: 0.0241

Gnomad4 OTH exome AF: 0.0366

GnomAD4 genome AF: 0.0333 AC: 5076 AN: 152226 Hom.: 119 Cov.: 33 AF XY: 0.0332 AC XY: 2468 AN XY: 74434

Gnomad4 AFR AF: 0.0420

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00766

Gnomad4 FIN AF: 0.0321

Gnomad4 NFE AF: 0.0271

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0322 Hom.: 8

Bravo AF: 0.0355

Asia WGS AF: 0.00866 AC: 30 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	-0.86
CADD	Benign	0.16
DANN	Benign	0.26

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: rs73823859; hg19: chr4-69962101;