rs28365062

chr4-69098553-A-Gchr4-69098553-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001074.4(UGT2B7):c.735A>G(p.Thr245=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,604,518 control chromosomes in the GnomAD database, including 18,331 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 0.16 (2152 hom., cov: 30)
  • Exomes 𝑓: 0.14 (16179 hom.)
• Consequence: UGT2B7 NM_001074.4 synonymous
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 0.276

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.276 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B7	NM_001074.4	c.735A>G	p.Thr245=	synonymous_variant	2/6	ENST00000305231.12
UGT2B7	NM_001330719.2	c.735A>G	p.Thr245=	synonymous_variant	2/5
UGT2B7	NM_001349568.2	c.-13A>G		5_prime_UTR_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B7	ENST00000305231.12	c.735A>G	p.Thr245=	synonymous_variant	2/6	1	NM_001074.4	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 23917 AN: 150748 Hom.: 2149 Cov.: 30

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0477

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.177

GnomAD3 exomes AF: 0.172 AC: 42073 AN: 244836 Hom.: 4901 AF XY: 0.162 AC XY: 21491 AN XY: 132718

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.383

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.0437

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.137

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.138 AC: 200354 AN: 1453658 Hom.: 16179 Cov.: 43 AF XY: 0.136 AC XY: 98393 AN XY: 723090

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.0609

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.159 AC: 23936 AN: 150860 Hom.: 2152 Cov.: 30 AF XY: 0.165 AC XY: 12137 AN XY: 73594

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.0476

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.178

Alfa AF: 0.117 Hom.: 522

Bravo AF: 0.164

Asia WGS AF: 0.115 AC: 399 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	1.1
Dann	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs28365062; hg19: chr4-69964271; COSMIC: COSV59443088;