Genetic Variant UGT2B15:p.Lys523Thr (chr4-68647129-T-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_001076.4(UGT2B15):c.1568A>C(p.Lys523Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,613,218 control chromosomes in the GnomAD database, including 306,390 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 21143 hom., cov: 32)

Exomes 𝑓: 0.61 ( 285247 hom. )

Consequence

UGT2B15
NM_001076.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.61

Publications

53 publications found

Variant links:

Genes affected

UGT2B15 (HGNC:12546): (UDP glucuronosyltransferase family 2 member B15) This gene encodes a glycosyltransferase that is invovled in the metabolism and elimination of toxic compounts, both endogenous and of xenobiotic origin. This gene plays a role in the regulation of estrogens and androgens. This locus is present in a cluster of similar genes and pseudogenes on chromosome 4. [provided by RefSeq, Aug 2016]

UGT2B15 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 (MetaRNN=3.9870465E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B15	NM_001076.4 link	c.1568A>C	p.Lys523Thr	missense_variant	Exon 6 of 6	ENST00000338206.6	NP_001067.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B15	ENST00000338206.6 link	c.1568A>C	p.Lys523Thr	missense_variant	Exon 6 of 6	1	NM_001076.4	ENSP00000341045.5		P54855

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73997

AN:

151806

Hom.:

21142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.665

Gnomad AMR

AF:

0.509

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.519

Gnomad FIN

AF:

0.617

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.470

GnomAD2 exomes

AF:

0.550

AC:

137921

AN:

250942

AF XY:

0.556

show subpopulations

Gnomad AFR exome

AF:

0.192

Gnomad AMR exome

AF:

0.554

Gnomad ASJ exome

AF:

0.608

Gnomad EAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.628

Gnomad NFE exome

AF:

0.646

Gnomad OTH exome

AF:

0.570

GnomAD4 exome

AF:

0.613

AC:

895733

AN:

1461290

Hom.:

285247

Cov.:

AF XY:

0.611

AC XY:

444472

AN XY:

726932

show subpopulations

African (AFR)

AF:

0.189

AC:

6325

AN:

33450

American (AMR)

AF:

0.549

AC:

24530

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.614

AC:

16050

AN:

26122

East Asian (EAS)

AF:

0.171

AC:

6787

AN:

39698

South Asian (SAS)

AF:

0.521

AC:

44913

AN:

86178

European-Finnish (FIN)

AF:

0.629

AC:

33588

AN:

53408

Middle Eastern (MID)

AF:

0.548

AC:

3158

AN:

5760

European-Non Finnish (NFE)

AF:

0.653

AC:

725914

AN:

1111612

Other (OTH)

AF:

0.571

AC:

34468

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

19526

39052

58579

78105

97631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18636

37272

55908

74544

93180

<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:

0.487

AC:

74024

AN:

151928

Hom.:

21143

Cov.:

AF XY:

0.485

AC XY:

35988

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.209

AC:

8677

AN:

41456

American (AMR)

AF:

0.510

AC:

7776

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.618

AC:

2140

AN:

3462

East Asian (EAS)

AF:

0.179

AC:

926

AN:

5178

South Asian (SAS)

AF:

0.519

AC:

2491

AN:

4800

European-Finnish (FIN)

AF:

0.617

AC:

6508

AN:

10546

Middle Eastern (MID)

AF:

0.551

AC:

161

AN:

292

European-Non Finnish (NFE)

AF:

0.644

AC:

43755

AN:

67924

Other (OTH)

AF:

0.468

AC:

989

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1637

3274

4912

6549

8186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<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:

0.575

Hom.:

11457

Bravo

AF:

0.463

TwinsUK

AF:

0.650

AC:

2411

ALSPAC

AF:

0.654

AC:

2519

ESP6500AA

AF:

0.224

AC:

989

ESP6500EA

AF:

0.633

AC:

5436

ExAC

AF:

0.545

AC:

66222

Asia WGS

AF:

0.363

AC:

1265

AN:

3478

EpiCase

AF:

0.634

EpiControl

AF:

0.639

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.011

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.0046

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.043

MetaRNN

Benign

0.0000040

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.045

PhyloP100

-1.6

PrimateAI

Benign

0.24

PROVEAN

Benign

1.8

REVEL

Benign

0.038

Sift

Benign

1.0

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.043

MPC

0.020

ClinPred

0.0025

GERP RS

-0.32

Varity_R

0.028

gMVP

0.093

Mutation Taster

=99/1

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