Variant 4-69096657-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001074.4(UGT2B7):c.137T>C(p.Leu46Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00441 in 1,614,008 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 25 hom. )

Consequence

UGT2B7
NM_001074.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 5.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036030054).

BP6

Variant 4-69096657-T-C is Benign according to our data. Variant chr4-69096657-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 718812.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UGT2B7	NM_001074.4 linkuse as main transcript	c.137T>C	p.Leu46Pro	missense_variant	1/6	ENST00000305231.12
UGT2B7	NM_001330719.2 linkuse as main transcript	c.137T>C	p.Leu46Pro	missense_variant	1/5
UGT2B7	NM_001349568.2 linkuse as main transcript	c.-26-1883T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B7	ENST00000305231.12 linkuse as main transcript	c.137T>C	p.Leu46Pro	missense_variant	1/6	1	NM_001074.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

413

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00509

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00262

AC:

658

AN:

251426

Hom.:

AF XY:

0.00256

AC XY:

348

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00480

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00459

AC:

6710

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00453

AC XY:

3292

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000626

Gnomad4 FIN exome

AF:

0.00228

Gnomad4 NFE exome

AF:

0.00562

Gnomad4 OTH exome

AF:

0.00318

GnomAD4 genome

AF:

0.00271

AC:

413

AN:

152254

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00509

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00455

Hom.:

Bravo

AF:

0.00274

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.00270

AC:

328

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00463

EpiControl

AF:

0.00433

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 05, 2018

- -

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

Pathogenic

0.98

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Pathogenic

0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.70

D;.;.

Eigen

Uncertain

0.19

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.036

T;T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Pathogenic

4.6

H;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-6.5

D;D;.

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.73

MVP

0.63

MPC

0.22

ClinPred

0.14

GERP RS

1.2

Varity_R

0.97

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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