dbSNP rs12647681: UGT2B7:c.721+201A>C (chr4-69097442-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001074.4(UGT2B7):c.721+201A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,388 control chromosomes in the GnomAD database, including 26,056 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 ( 26056 hom., cov: 31)

Consequence

UGT2B7
NM_001074.4 intron

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 0.0170

Publications

1 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:58802):

ENSG00000299782 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
UGT2B7	NM_001074.4 link	c.721+201A>C	intron_variant	Intron 1 of 5	ENST00000305231.12	NP_001065.2
UGT2B7	NM_001330719.2 link	c.721+201A>C	intron_variant	Intron 1 of 4		NP_001317648.1
UGT2B7	NM_001349568.2 link	c.-26-1098A>C	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.721+201A>C		intron_variant	Intron 1 of 5	1	NM_001074.4	ENSP00000304811.7

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87067

AN:

151266

Hom.:

26008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.712

Gnomad AMI

AF:

0.481

Gnomad AMR

AF:

0.658

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.701

Gnomad SAS

AF:

0.603

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.571

Gnomad NFE

AF:

0.468

Gnomad OTH

AF:

0.588

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.576

AC:

87172

AN:

151388

Hom.:

26056

Cov.:

AF XY:

0.584

AC XY:

43201

AN XY:

73914

show subpopulations

African (AFR)

AF:

0.712

AC:

29409

AN:

41306

American (AMR)

AF:

0.659

AC:

10010

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1770

AN:

3462

East Asian (EAS)

AF:

0.700

AC:

3588

AN:

5124

South Asian (SAS)

AF:

0.604

AC:

2900

AN:

4800

European-Finnish (FIN)

AF:

0.571

AC:

5986

AN:

10480

Middle Eastern (MID)

AF:

0.583

AC:

169

AN:

290

European-Non Finnish (NFE)

AF:

0.468

AC:

31666

AN:

67718

Other (OTH)

AF:

0.588

AC:

1241

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1825

3650

5474

7299

9124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.514

Hom.:

4250

Bravo

AF:

0.590

Asia WGS

AF:

0.656

AC:

2279

AN:

3476

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

-0.92

CADD

Benign

2.4

(source)

DANN

Benign

0.39

PhyloP100

0.017

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over