dbSNP rs73823859: UGT2B7:c.-26-2157G>A (chr4-69096383-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001349568.2(UGT2B7):c.-26-2157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 1,366,818 control chromosomes in the GnomAD database, including 758 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 ( 119 hom., cov: 33)

Exomes 𝑓: 0.026 ( 639 hom. )

Consequence

UGT2B7
NM_001349568.2 intron

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -1.38

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0996 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001349568.2 link	c.-26-2157G>A	intron_variant	Intron 2 of 6		NP_001336497.1
UGT2B7	NM_001074.4 link	c.-138G>A	upstream_gene_variant		ENST00000305231.12	NP_001065.2	P16662
UGT2B7	NM_001330719.2 link	c.-138G>A	upstream_gene_variant			NP_001317648.1	P16662E9PBP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12 link	c.-138G>A		upstream_gene_variant		1	NM_001074.4	ENSP00000304811.7		P16662

Frequencies

GnomAD3 genomes

AF:

0.0334

AC:

5084

AN:

152108

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0420

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0332

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00849

Gnomad FIN

AF:

0.0321

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0271

Gnomad OTH

AF:

0.0469

GnomAD4 exome

AF:

0.0259

AC:

31410

AN:

1214592

Hom.:

639

AF XY:

0.0257

AC XY:

15558

AN XY:

605058

show subpopulations

Gnomad4 AFR exome

AF:

0.0487

Gnomad4 AMR exome

AF:

0.0238

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.0000537

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.0283

Gnomad4 NFE exome

AF:

0.0241

Gnomad4 OTH exome

AF:

0.0366

GnomAD4 genome

AF:

0.0333

AC:

5076

AN:

152226

Hom.:

119

Cov.:

AF XY:

0.0332

AC XY:

2468

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0420

Gnomad4 AMR

AF:

0.0331

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00766

Gnomad4 FIN

AF:

0.0321

Gnomad4 NFE

AF:

0.0271

Gnomad4 OTH

AF:

0.0464

Alfa

AF:

0.0322

Hom.:

Bravo

AF:

0.0355

Asia WGS

AF:

0.00866

AC:

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

-0.86

CADD

Benign

0.16

DANN

Benign

0.26

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