dbSNP rs7439366: UGT2B7:p.Tyr268His (chr4-69098620-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

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

Publications

257 publications found

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:

ENSG00000299782 (HGNC:):

ENSG00000299782 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4 link	c.802T>C	p.Tyr268His	missense_variant	Exon 2 of 6	ENST00000305231.12	NP_001065.2	P16662
UGT2B7	NM_001330719.2 link	c.802T>C	p.Tyr268His	missense_variant	Exon 2 of 5		NP_001317648.1	P16662E9PBP8
UGT2B7	NM_001349568.2 link	c.55T>C	p.Tyr19His	missense_variant	Exon 3 of 7		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12 link	c.802T>C	p.Tyr268His	missense_variant	Exon 2 of 6	1	NM_001074.4	ENSP00000304811.7		P16662

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

GnomAD2 exomes

AF:

0.564

AC:

140844

AN:

249590

AF XY:

0.554

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 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

African (AFR)

AF:

0.716

AC:

23831

AN:

33302

American (AMR)

AF:

0.713

AC:

31691

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

13267

AN:

26058

East Asian (EAS)

AF:

0.703

AC:

27824

AN:

39570

South Asian (SAS)

AF:

0.567

AC:

48660

AN:

85816

European-Finnish (FIN)

AF:

0.578

AC:

30866

AN:

53390

Middle Eastern (MID)

AF:

0.527

AC:

3036

AN:

5760

European-Non Finnish (NFE)

AF:

0.459

AC:

510152

AN:

1110578

Other (OTH)

AF:

0.517

AC:

31179

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

20945

41889

62834

83778

104723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15510

31020

46530

62040

77550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.576

AC:

86973

AN:

151098

Hom.:

25993

Cov.:

AF XY:

0.584

AC XY:

43110

AN XY:

73774

show subpopulations

African (AFR)

AF:

0.712

AC:

29289

AN:

41162

American (AMR)

AF:

0.659

AC:

10016

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1769

AN:

3456

East Asian (EAS)

AF:

0.697

AC:

3543

AN:

5080

South Asian (SAS)

AF:

0.604

AC:

2896

AN:

4796

European-Finnish (FIN)

AF:

0.573

AC:

5992

AN:

10464

Middle Eastern (MID)

AF:

0.577

AC:

165

AN:

286

European-Non Finnish (NFE)

AF:

0.468

AC:

31634

AN:

67660

Other (OTH)

AF:

0.587

AC:

1230

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1762

3524

5285

7047

8809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.517

Hom.:

12758

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

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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.4

(source)

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

PhyloP100

2.0

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over