rs28365063

chr4-69096892-A-Gchr4-69096892-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.372A>G(p.Arg124=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,611,946 control chromosomes in the GnomAD database, including 23,270 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 0.15 (1877 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21393 hom.)
• Consequence: UGT2B7 NM_001074.4 synonymous
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0270

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=-0.91).
• BP7: Synonymous conserved (PhyloP=-0.027 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B7	NM_001074.4	c.372A>G	p.Arg124=	synonymous_variant	1/6	ENST00000305231.12
UGT2B7	NM_001330719.2	c.372A>G	p.Arg124=	synonymous_variant	1/5
UGT2B7	NM_001349568.2	c.-26-1648A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B7	ENST00000305231.12	c.372A>G	p.Arg124=	synonymous_variant	1/6	1	NM_001074.4	P1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22423 AN: 152016 Hom.: 1876 Cov.: 32

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.149

GnomAD3 exomes AF: 0.158 AC: 39244 AN: 248336 Hom.: 3426 AF XY: 0.163 AC XY: 21880 AN XY: 134540

Gnomad AFR exome AF: 0.0797

Gnomad AMR exome AF: 0.0939

Gnomad ASJ exome AF: 0.191

Gnomad EAS exome AF: 0.184

Gnomad SAS exome AF: 0.148

Gnomad FIN exome AF: 0.205

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.168 AC: 245478 AN: 1459812 Hom.: 21393 Cov.: 32 AF XY: 0.169 AC XY: 122583 AN XY: 726152

Gnomad4 AFR exome AF: 0.0847

Gnomad4 AMR exome AF: 0.0965

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.147 AC: 22436 AN: 152134 Hom.: 1877 Cov.: 32 AF XY: 0.147 AC XY: 10905 AN XY: 74378

Gnomad4 AFR AF: 0.0868

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.150

Alfa AF: 0.168 Hom.: 2869

Bravo AF: 0.138

Asia WGS AF: 0.158 AC: 550 AN: 3478

EpiCase AF: 0.179

EpiControl AF: 0.175

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	-0.91
Cadd	Benign	0.84
Dann	Benign	0.58

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: rs28365063; hg19: chr4-69962610; COSMIC: COSV59442457;