Genetic Variant UGT2B7:c.1091-154C>G (chr4-69107949-C-G) – 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.1091-154C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,032 control chromosomes in the GnomAD database, including 27,892 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 ( 27892 hom., cov: 32)

Consequence

UGT2B7
NM_001074.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.416

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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new If you want to explore the variant's impact on the transcript NM_001074.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 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.1091-154C>G	intron	N/A	NP_001065.2	P16662
UGT2B7	NM_001330719.2		c.1090+687C>G	intron	N/A	NP_001317648.1	E9PBP8
UGT2B7	NM_001349568.2		c.344-154C>G	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.1091-154C>G	intron	N/A	ENSP00000304811.7	P16662
UGT2B7	ENST00000868341.1		c.1187-154C>G	intron	N/A	ENSP00000538400.1
UGT2B7	ENST00000868343.1		c.1091-154C>G	intron	N/A	ENSP00000538402.1

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89688

AN:

151914

Hom.:

27843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.664

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.701

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.575

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.598

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

GnomAD4 genome

AF:

0.591

AC:

89793

AN:

152032

Hom.:

27892

Cov.:

AF XY:

0.598

AC XY:

44459

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.766

AC:

31763

AN:

41472

American (AMR)

AF:

0.665

AC:

10145

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1776

AN:

3470

East Asian (EAS)

AF:

0.701

AC:

3621

AN:

5168

South Asian (SAS)

AF:

0.555

AC:

2675

AN:

4818

European-Finnish (FIN)

AF:

0.575

AC:

6068

AN:

10554

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.469

AC:

31860

AN:

67970

Other (OTH)

AF:

0.599

AC:

1267

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1764

3527

5291

7054

8818

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:

0.379

Hom.:

1018

Bravo

AF:

0.607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.2

(source)

DANN

Benign

0.33

PhyloP100

0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Computational scores

Splicing

Publications

Other links and lift over