Genetic Variant 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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001074.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UGT2B7	NM_001074.4	MANE Select	c.721+201A>C	intron	N/A	NP_001065.2
UGT2B7	NM_001330719.2		c.721+201A>C	intron	N/A	NP_001317648.1
UGT2B7	NM_001349568.2		c.-26-1098A>C	intron	N/A	NP_001336497.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UGT2B7	ENST00000305231.12	TSL:1 MANE Select	c.721+201A>C	intron	N/A	ENSP00000304811.7
UGT2B7	ENST00000508661.5	TSL:2	c.721+201A>C	intron	N/A	ENSP00000427659.1
UGT2B7	ENST00000622664.1	TSL:5	c.721+201A>C	intron	N/A	ENSP00000483172.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over