Variant chr4-69096731-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001074.4(UGT2B7):c.211G>T(p.Ala71Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0056 in 1,613,916 control chromosomes in the GnomAD database, including 560 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0066 ( 57 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 503 hom. )

Consequence

UGT2B7
NM_001074.4 missense

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -2.27

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016804338).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UGT2B7	NM_001074.4 linkuse as main transcript	c.211G>T	p.Ala71Ser	missense_variant	1/6	ENST00000305231.12
UGT2B7	NM_001330719.2 linkuse as main transcript	c.211G>T	p.Ala71Ser	missense_variant	1/5
UGT2B7	NM_001349568.2 linkuse as main transcript	c.-26-1809G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B7	ENST00000305231.12 linkuse as main transcript	c.211G>T	p.Ala71Ser	missense_variant	1/6	1	NM_001074.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00667

AC:

1015

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00761

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.0139

AC:

3489

AN:

251152

Hom.:

216

AF XY:

0.0125

AC XY:

1694

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.143

Gnomad SAS exome

AF:

0.00242

Gnomad FIN exome

AF:

0.0130

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.00588

GnomAD4 exome

AF:

0.00549

AC:

8023

AN:

1461730

Hom.:

503

Cov.:

AF XY:

0.00535

AC XY:

3889

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.00293

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.000178

Gnomad4 OTH exome

AF:

0.00735

GnomAD4 genome

AF:

0.00664

AC:

1011

AN:

152186

Hom.:

Cov.:

AF XY:

0.00798

AC XY:

594

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00754

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.138

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0337

Hom.:

3768

Bravo

AF:

0.00796

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0127

AC:

1543

Asia WGS

AF:

0.0400

AC:

137

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

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

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.014

DANN

Benign

0.42

DEOGEN2

Benign

0.097

T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.13

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.84

N;N;.

REVEL

Benign

0.045

Sift

Benign

0.28

T;T;.

Sift4G

Benign

0.40

T;T;T

Polyphen

0.12

B;B;.

Vest4

0.040

MPC

0.026

ClinPred

0.019

GERP RS

-3.9

Varity_R

0.054

gMVP

0.070

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