Genetic Variant UGT2B7:p.Leu353Leu (chr4-69107231-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001074.4(UGT2B7):c.1059C>G(p.Leu353Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,606,936 control chromosomes in the GnomAD database, including 209,705 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 0.59 ( 27852 hom., cov: 31)

Exomes 𝑓: 0.49 ( 181853 hom. )

Consequence

UGT2B7
NM_001074.4 synonymous

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -2.87

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP7

Synonymous conserved (PhyloP=-2.87 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001074.4 link	c.1059C>G	p.Leu353Leu	synonymous_variant	Exon 4 of 6	ENST00000305231.12	NP_001065.2	P16662
UGT2B7	NM_001330719.2 link	c.1059C>G	p.Leu353Leu	synonymous_variant	Exon 4 of 5		NP_001317648.1	P16662E9PBP8
UGT2B7	NM_001349568.2 link	c.312C>G	p.Leu104Leu	synonymous_variant	Exon 5 of 7		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12 link	c.1059C>G	p.Leu353Leu	synonymous_variant	Exon 4 of 6	1	NM_001074.4	ENSP00000304811.7		P16662

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89584

AN:

151736

Hom.:

27802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.664

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.702

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.574

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.597

GnomAD3 exomes

AF:

0.562

AC:

140529

AN:

249856

Hom.:

41114

AF XY:

0.549

AC XY:

74128

AN XY:

135084

show subpopulations

Gnomad AFR exome

AF:

0.770

Gnomad AMR exome

AF:

0.722

Gnomad ASJ exome

AF:

0.510

Gnomad EAS exome

AF:

0.704

Gnomad SAS exome

AF:

0.519

Gnomad FIN exome

AF:

0.583

Gnomad NFE exome

AF:

0.475

Gnomad OTH exome

AF:

0.539

GnomAD4 exome

AF:

0.492

AC:

716176

AN:

1455080

Hom.:

181853

Cov.:

AF XY:

0.492

AC XY:

355969

AN XY:

724032

show subpopulations

Gnomad4 AFR exome

AF:

0.773

Gnomad4 AMR exome

AF:

0.715

Gnomad4 ASJ exome

AF:

0.510

Gnomad4 EAS exome

AF:

0.703

Gnomad4 SAS exome

AF:

0.517

Gnomad4 FIN exome

AF:

0.579

Gnomad4 NFE exome

AF:

0.459

Gnomad4 OTH exome

AF:

0.517

GnomAD4 genome

AF:

0.591

AC:

89691

AN:

151856

Hom.:

27852

Cov.:

AF XY:

0.598

AC XY:

44404

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.766

Gnomad4 AMR

AF:

0.665

Gnomad4 ASJ

AF:

0.511

Gnomad4 EAS

AF:

0.701

Gnomad4 SAS

AF:

0.555

Gnomad4 FIN

AF:

0.574

Gnomad4 NFE

AF:

0.469

Gnomad4 OTH

AF:

0.598

Alfa

AF:

0.452

Hom.:

4410

Bravo

AF:

0.607

Asia WGS

AF:

0.637

AC:

2215

AN:

3478

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

-0.95

CADD

Benign

0.41

DANN

Benign

0.48

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