Genetic Variant UGT2B7:c.1091-129C>T (chr4-69107974-C-T) – 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.1091-129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,241,970 control chromosomes in the GnomAD database, including 164,696 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.59 ( 27924 hom., cov: 32)

Exomes 𝑓: 0.49 ( 136772 hom. )

Consequence

UGT2B7
NM_001074.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.295

Publications

2 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=-1.04).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 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	UniProt
UGT2B7	NM_001074.4	MANE Select	c.1091-129C>T	intron	N/A	NP_001065.2	P16662
UGT2B7	NM_001330719.2		c.1090+712C>T	intron	N/A	NP_001317648.1	E9PBP8
UGT2B7	NM_001349568.2		c.344-129C>T	intron	N/A	NP_001336497.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
UGT2B7	ENST00000305231.12	TSL:1 MANE Select	c.1091-129C>T	intron	N/A	ENSP00000304811.7	P16662
UGT2B7	ENST00000868341.1		c.1187-129C>T	intron	N/A	ENSP00000538400.1
UGT2B7	ENST00000868343.1		c.1091-129C>T	intron	N/A	ENSP00000538402.1

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89721

AN:

151856

Hom.:

27873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.767

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.664

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.702

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.576

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.598

GnomAD4 exome

AF:

0.494

AC:

538022

AN:

1089996

Hom.:

136772

AF XY:

0.493

AC XY:

271668

AN XY:

550614

show subpopulations

African (AFR)

AF:

0.769

AC:

18925

AN:

24618

American (AMR)

AF:

0.704

AC:

20481

AN:

29092

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

10037

AN:

19730

East Asian (EAS)

AF:

0.704

AC:

26104

AN:

37070

South Asian (SAS)

AF:

0.520

AC:

34435

AN:

66282

European-Finnish (FIN)

AF:

0.581

AC:

27431

AN:

47248

Middle Eastern (MID)

AF:

0.526

AC:

1792

AN:

3410

European-Non Finnish (NFE)

AF:

0.459

AC:

374367

AN:

815404

Other (OTH)

AF:

0.519

AC:

24450

AN:

47142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

12924

25848

38773

51697

64621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10300

20600

30900

41200

51500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.591

AC:

89830

AN:

151974

Hom.:

27924

Cov.:

AF XY:

0.599

AC XY:

44492

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.767

AC:

31811

AN:

41462

American (AMR)

AF:

0.665

AC:

10145

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1775

AN:

3470

East Asian (EAS)

AF:

0.701

AC:

3616

AN:

5156

South Asian (SAS)

AF:

0.555

AC:

2675

AN:

4818

European-Finnish (FIN)

AF:

0.576

AC:

6071

AN:

10548

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.469

AC:

31858

AN:

67950

Other (OTH)

AF:

0.599

AC:

1262

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1779

3558

5336

7115

8894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.574

Hom.:

7463

Bravo

AF:

0.607

Asia WGS

AF:

0.639

AC:

2219

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

3.5

(source)

DANN

Benign

0.66

PhyloP100

-0.29

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over