dbSNP rs28365063: UGT2B7:p.Arg124Arg (chr4-69096892-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001074.4(UGT2B7):c.372A>G(p.Arg124Arg) 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

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.0270

Variant links:

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]

UGT2B7 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4 link	c.372A>G	p.Arg124Arg	synonymous_variant	Exon 1 of 6	ENST00000305231.12	NP_001065.2	P16662
UGT2B7	NM_001330719.2 link	c.372A>G	p.Arg124Arg	synonymous_variant	Exon 1 of 5		NP_001317648.1	P16662E9PBP8
UGT2B7	NM_001349568.2 link	c.-26-1648A>G		intron_variant	Intron 2 of 6		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12 link	c.372A>G	p.Arg124Arg	synonymous_variant	Exon 1 of 6	1	NM_001074.4	ENSP00000304811.7		P16662

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22423

AN:

152016

Hom.:

1876

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.169

AC XY:

122583

AN XY:

726152

show subpopulations

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.:

AF XY:

0.147

AC XY:

10905

AN XY:

74378

show subpopulations

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

LINK: link

Submissions by phenotype

Tramadol response

Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

- 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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over