Variant rs7439366 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.802T>C(p.Tyr268His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,610,326 control chromosomes in the GnomAD database, including 209,146 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.58 ( 25993 hom., cov: 30)

Exomes 𝑓: 0.49 ( 183153 hom. )

Consequence

UGT2B7
NM_001074.4 missense

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 2.01

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=9.89177E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UGT2B7	NM_001074.4 linkuse as main transcript	c.802T>C	p.Tyr268His	missense_variant	2/6	ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2 linkuse as main transcript	c.802T>C	p.Tyr268His	missense_variant	2/5		NP_001317648.1
UGT2B7	NM_001349568.2 linkuse as main transcript	c.55T>C	p.Tyr19His	missense_variant	3/7		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12 linkuse as main transcript	c.802T>C	p.Tyr268His	missense_variant	2/6	1	NM_001074.4	ENSP00000304811	P1

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

86872

AN:

150978

Hom.:

25947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.711

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.659

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.698

Gnomad SAS

AF:

0.603

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.572

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.586

GnomAD3 exomes

AF:

0.564

AC:

140844

AN:

249590

Hom.:

41202

AF XY:

0.554

AC XY:

74792

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.714

Gnomad AMR exome

AF:

0.720

Gnomad ASJ exome

AF:

0.508

Gnomad EAS exome

AF:

0.704

Gnomad SAS exome

AF:

0.570

Gnomad FIN exome

AF:

0.583

Gnomad NFE exome

AF:

0.475

Gnomad OTH exome

AF:

0.539

GnomAD4 exome

AF:

0.494

AC:

720506

AN:

1459228

Hom.:

183153

Cov.:

AF XY:

0.495

AC XY:

359042

AN XY:

725826

show subpopulations

Gnomad4 AFR exome

AF:

0.716

Gnomad4 AMR exome

AF:

0.713

Gnomad4 ASJ exome

AF:

0.509

Gnomad4 EAS exome

AF:

0.703

Gnomad4 SAS exome

AF:

0.567

Gnomad4 FIN exome

AF:

0.578

Gnomad4 NFE exome

AF:

0.459

Gnomad4 OTH exome

AF:

0.517

GnomAD4 genome

AF:

0.576

AC:

86973

AN:

151098

Hom.:

25993

Cov.:

AF XY:

0.584

AC XY:

43110

AN XY:

73774

show subpopulations

Gnomad4 AFR

AF:

0.712

Gnomad4 AMR

AF:

0.659

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.697

Gnomad4 SAS

AF:

0.604

Gnomad4 FIN

AF:

0.573

Gnomad4 NFE

AF:

0.468

Gnomad4 OTH

AF:

0.587

Alfa

AF:

0.507

Hom.:

8904

Bravo

AF:

0.590

TwinsUK

AF:

0.452

AC:

1676

ALSPAC

AF:

0.451

AC:

1739

ESP6500AA

AF:

0.282

AC:

1242

ESP6500EA

AF:

0.125

AC:

1078

ExAC

AF:

0.560

AC:

67949

Asia WGS

AF:

0.655

AC:

2275

AN:

3478

EpiCase

AF:

0.490

EpiControl

AF:

0.481

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

0.12

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.4

DANN

Benign

0.68

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0096

LIST_S2

Benign

0.33

T;T;T;T

MetaRNN

Benign

0.0000099

T;T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

3.3

N;N;N;.

REVEL

Benign

0.066

Sift

Benign

0.56

T;T;T;.

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.0

.;.;B;.

Vest4

0.11, 0.043, 0.059

MPC

0.025

ClinPred

0.00043

GERP RS

1.8

Varity_R

0.023

gMVP

0.41

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