Variant chr4-69098673-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001074.4(UGT2B7):c.855C>A(p.Ala285Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,610,488 control chromosomes in the GnomAD database, including 907 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 0.033 ( 116 hom., cov: 32)

Exomes 𝑓: 0.026 ( 791 hom. )

Consequence

UGT2B7
NM_001074.4 synonymous

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.297

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:

UGT2B7 (HGNC:):

UGT2B7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP7

Synonymous conserved (PhyloP=-0.297 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B7	NM_001074.4 linkuse as main transcript	c.855C>A	p.Ala285Ala	synonymous_variant	2/6	ENST00000305231.12	NP_001065.2	P16662
UGT2B7	NM_001330719.2 linkuse as main transcript	c.855C>A	p.Ala285Ala	synonymous_variant	2/5		NP_001317648.1	P16662E9PBP8
UGT2B7	NM_001349568.2 linkuse as main transcript	c.108C>A	p.Ala36Ala	synonymous_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.855C>A	p.Ala285Ala	synonymous_variant	2/6	1	NM_001074.4	ENSP00000304811.7		P16662

Frequencies

GnomAD3 genomes

AF:

0.0333

AC:

5064

AN:

151884

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0419

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0331

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.0319

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0479

GnomAD3 exomes

AF:

0.0288

AC:

7139

AN:

248162

Hom.:

197

AF XY:

0.0285

AC XY:

3834

AN XY:

134344

show subpopulations

Gnomad AFR exome

AF:

0.0459

Gnomad AMR exome

AF:

0.0211

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.000166

Gnomad SAS exome

AF:

0.00990

Gnomad FIN exome

AF:

0.0291

Gnomad NFE exome

AF:

0.0290

Gnomad OTH exome

AF:

0.0403

GnomAD4 exome

AF:

0.0262

AC:

38279

AN:

1458486

Hom.:

791

Cov.:

AF XY:

0.0260

AC XY:

18885

AN XY:

725626

show subpopulations

Gnomad4 AFR exome

AF:

0.0478

Gnomad4 AMR exome

AF:

0.0220

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.0282

Gnomad4 NFE exome

AF:

0.0245

Gnomad4 OTH exome

AF:

0.0364

GnomAD4 genome

AF:

0.0333

AC:

5056

AN:

152002

Hom.:

116

Cov.:

AF XY:

0.0331

AC XY:

2457

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0419

Gnomad4 AMR

AF:

0.0330

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00767

Gnomad4 FIN

AF:

0.0319

Gnomad4 NFE

AF:

0.0270

Gnomad4 OTH

AF:

0.0474

Alfa

AF:

0.0374

Hom.:

Bravo

AF:

0.0354

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.0330

EpiControl

AF:

0.0376

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

BayesDel_noAF

Benign

-0.38

CADD

Benign

5.0

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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