Genetic Variant NM_001349568.2:c.-26-2180T>C (chr4-69096360-T-C) – 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.-26-2180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,130,256 control chromosomes in the GnomAD database, including 149,632 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 0.58 ( 26313 hom., cov: 32)

Exomes 𝑓: 0.49 ( 123319 hom. )

Consequence

UGT2B7
NM_001349568.2 intron

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -1.67

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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
UGT2B7	NM_001349568.2 link	c.-26-2180T>C	intron_variant	Intron 2 of 6		NP_001336497.1
UGT2B7	NM_001074.4 link	c.-161T>C	upstream_gene_variant		ENST00000305231.12	NP_001065.2	P16662
UGT2B7	NM_001330719.2 link	c.-161T>C	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.-161T>C		upstream_gene_variant		1	NM_001074.4	ENSP00000304811.7		P16662

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87599

AN:

151876

Hom.:

26267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.713

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.659

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.702

Gnomad SAS

AF:

0.603

Gnomad FIN

AF:

0.574

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.588

GnomAD4 exome

AF:

0.494

AC:

483291

AN:

978262

Hom.:

123319

AF XY:

0.496

AC XY:

243703

AN XY:

491698

show subpopulations

Gnomad4 AFR exome

AF:

0.714

Gnomad4 AMR exome

AF:

0.683

Gnomad4 ASJ exome

AF:

0.510

Gnomad4 EAS exome

AF:

0.704

Gnomad4 SAS exome

AF:

0.569

Gnomad4 FIN exome

AF:

0.578

Gnomad4 NFE exome

AF:

0.460

Gnomad4 OTH exome

AF:

0.519

GnomAD4 genome

AF:

0.577

AC:

87700

AN:

151994

Hom.:

26313

Cov.:

AF XY:

0.586

AC XY:

43528

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.713

Gnomad4 AMR

AF:

0.660

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.702

Gnomad4 SAS

AF:

0.604

Gnomad4 FIN

AF:

0.574

Gnomad4 NFE

AF:

0.469

Gnomad4 OTH

AF:

0.588

Alfa

AF:

0.506

Hom.:

20999

Bravo

AF:

0.590

Asia WGS

AF:

0.657

AC:

2283

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

-0.88

CADD

Benign

0.11

DANN

Benign

0.60

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