Genetic Variant UGT2B17:p.Arg470His (chr4-68537809-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001077.4(UGT2B17):c.1409G>A(p.Arg470His) variant causes a missense change. The variant allele was found at a frequency of 0.0000138 in 1,379,408 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000079 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000014 ( 6 hom. )

Consequence

UGT2B17
NM_001077.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.33

Publications

1 publications found

Variant links:

Genes affected

UGT2B17 (HGNC:12547): (UDP glucuronosyltransferase family 2 member B17) This gene encodes a member of the uridine diphosphoglucuronosyltransferase protein family. The encoded enzyme catalyzes the transfer of glucuronic acid from uridine diphosphoglucuronic acid to a diverse array of substrates including steroid hormones and lipid-soluble drugs. This process, known as glucuronidation, is an intermediate step in the metabolism of steroids. Copy number variation in this gene is associated with susceptibility to osteoporosis.[provided by RefSeq, Apr 2010]

UGT2B17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B17	NM_001077.4	MANE Select	c.1409G>A	p.Arg470His	missense	Exon 7 of 7	NP_001068.1	O75795

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UGT2B17	ENST00000317746.3	TSL:1 MANE Select	c.1409G>A	p.Arg470His	missense	Exon 7 of 7	ENSP00000320401.2	O75795
UGT2B17	ENST00000893234.1		c.1409G>A	p.Arg470His	missense	Exon 6 of 6	ENSP00000563293.1
UGT2B17	ENST00000950879.1		c.1277G>A	p.Arg426His	missense	Exon 5 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes

AF:

0.00000792

AC:

AN:

126320

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000167

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000493

AC:

AN:

202878

AF XY:

0.00000918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1253088

Hom.:

Cov.:

AF XY:

0.0000178

AC XY:

AN XY:

619240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30952

American (AMR)

AF:

0.00

AC:

AN:

38296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22654

East Asian (EAS)

AF:

0.00

AC:

AN:

10794

South Asian (SAS)

AF:

0.000122

AC:

AN:

57262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4896

European-Non Finnish (NFE)

AF:

0.00000703

AC:

AN:

995244

Other (OTH)

AF:

0.0000784

AC:

AN:

51044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00000792

AC:

AN:

126320

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

60206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36996

American (AMR)

AF:

0.00

AC:

AN:

12284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2974

East Asian (EAS)

AF:

0.00

AC:

AN:

1322

South Asian (SAS)

AF:

0.00

AC:

AN:

2728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.0000167

AC:

AN:

59730

Other (OTH)

AF:

0.00

AC:

AN:

1698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

-0.055

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0067

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.61

MutationAssessor

Pathogenic

3.3

PhyloP100

5.3

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.27

Sift

Benign

0.054

Sift4G

Benign

0.069

Vest4

0.42

MutPred

0.72

Loss of MoRF binding (P = 0.0116)

MVP

0.34

MPC

1.8

ClinPred

0.89

GERP RS

2.0

Varity_R

0.17

gMVP

0.23

Mutation Taster

=96/4

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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