Genetic Variant UGT2B7:c.870+148G>A (chr4-69098836-G-A) – 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.870+148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 1,336,300 control chromosomes in the GnomAD database, including 173,141 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 0.58 ( 26275 hom., cov: 32)

Exomes 𝑓: 0.49 ( 146866 hom. )

Consequence

UGT2B7
NM_001074.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.402

Publications

6 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:):

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=-0.86).

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_001074.4 link	c.870+148G>A	intron_variant	Intron 2 of 5	ENST00000305231.12	NP_001065.2	P16662
UGT2B7	NM_001330719.2 link	c.870+148G>A	intron_variant	Intron 2 of 4		NP_001317648.1	P16662E9PBP8
UGT2B7	NM_001349568.2 link	c.123+148G>A	intron_variant	Intron 3 of 6		NP_001336497.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B7	ENST00000305231.12 link	c.870+148G>A		intron_variant	Intron 2 of 5	1	NM_001074.4	ENSP00000304811.7		P16662

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87494

AN:

151626

Hom.:

26229

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:

0.575

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.587

GnomAD4 exome

AF:

0.490

AC:

580846

AN:

1184556

Hom.:

146866

AF XY:

0.492

AC XY:

290808

AN XY:

591290

show subpopulations

African (AFR)

AF:

0.716

AC:

18341

AN:

25616

American (AMR)

AF:

0.691

AC:

18038

AN:

26110

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

9669

AN:

19010

East Asian (EAS)

AF:

0.701

AC:

25776

AN:

36756

South Asian (SAS)

AF:

0.560

AC:

35796

AN:

63940

European-Finnish (FIN)

AF:

0.576

AC:

27440

AN:

47606

Middle Eastern (MID)

AF:

0.523

AC:

1784

AN:

3410

European-Non Finnish (NFE)

AF:

0.459

AC:

418474

AN:

912362

Other (OTH)

AF:

0.513

AC:

25528

AN:

49746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

13201

26402

39602

52803

66004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12360

24720

37080

49440

61800

<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:

0.577

AC:

87595

AN:

151744

Hom.:

26275

Cov.:

AF XY:

0.586

AC XY:

43458

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.713

AC:

29550

AN:

41446

American (AMR)

AF:

0.660

AC:

10038

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1773

AN:

3466

East Asian (EAS)

AF:

0.701

AC:

3621

AN:

5162

South Asian (SAS)

AF:

0.604

AC:

2909

AN:

4818

European-Finnish (FIN)

AF:

0.575

AC:

6069

AN:

10546

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.469

AC:

31777

AN:

67784

Other (OTH)

AF:

0.588

AC:

1240

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1827

3655

5482

7310

9137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.515

Hom.:

27446

Bravo

AF:

0.590

Asia WGS

AF:

0.657

AC:

2282

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

(source)

DANN

Benign

0.38

PhyloP100

-0.40

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over