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

Variant summary

Our verdict is Benign. The variant received -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

Publications

38 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 -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

GnomAD2 exomes

AF:

0.158

AC:

39244

AN:

248336

AF XY:

0.163

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 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

African (AFR)

AF:

0.0847

AC:

2820

AN:

33276

American (AMR)

AF:

0.0965

AC:

4275

AN:

44296

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

4949

AN:

26088

East Asian (EAS)

AF:

0.176

AC:

6996

AN:

39666

South Asian (SAS)

AF:

0.150

AC:

12822

AN:

85762

European-Finnish (FIN)

AF:

0.202

AC:

10778

AN:

53398

Middle Eastern (MID)

AF:

0.181

AC:

1044

AN:

5764

European-Non Finnish (NFE)

AF:

0.173

AC:

191890

AN:

1111260

Other (OTH)

AF:

0.164

AC:

9904

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

11661

23322

34983

46644

58305

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6710

13420

20130

26840

33550

<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:

0.147

AC:

22436

AN:

152134

Hom.:

1877

Cov.:

AF XY:

0.147

AC XY:

10905

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0868

AC:

3602

AN:

41514

American (AMR)

AF:

0.122

AC:

1870

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

661

AN:

3466

East Asian (EAS)

AF:

0.181

AC:

935

AN:

5178

South Asian (SAS)

AF:

0.157

AC:

760

AN:

4826

European-Finnish (FIN)

AF:

0.205

AC:

2165

AN:

10578

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.174

AC:

11830

AN:

67978

Other (OTH)

AF:

0.150

AC:

317

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

960

1920

2880

3840

4800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.163

Hom.:

6957

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

(source)

DANN

Benign

0.58

PhyloP100

-0.027

PromoterAI

0.070

Neutral

(source)

Mutation Taster

=100/0

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