Variant 4-68567944-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001077.4(UGT2B17):c.541G>A(p.Val181Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 1,380,688 control chromosomes in the GnomAD database, including 417 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 188 hom., cov: 20)

Exomes 𝑓: 0.00078 ( 229 hom. )

Consequence

UGT2B17
NM_001077.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.91

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039244294).

BP6

Variant 4-68567944-C-T is Benign according to our data. Variant chr4-68567944-C-T is described in ClinVar as [Benign]. Clinvar id is 787028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00785 (995/126722) while in subpopulation AFR AF= 0.0259 (962/37126). AF 95% confidence interval is 0.0246. There are 188 homozygotes in gnomad4. There are 471 alleles in male gnomad4 subpopulation. Median coverage is 20. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 188 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGT2B17	NM_001077.4 linkuse as main transcript	c.541G>A	p.Val181Ile	missense_variant	2/7	ENST00000317746.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2B17	ENST00000317746.3 linkuse as main transcript	c.541G>A	p.Val181Ile	missense_variant	2/7	1	NM_001077.4	P1
UGT2B17	ENST00000684088.1 linkuse as main transcript	c.-26-2224G>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00782

AC:

990

AN:

126650

Hom.:

186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00178

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000350

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00365

Gnomad NFE

AF:

0.0000335

Gnomad OTH

AF:

0.00404

GnomAD3 exomes

AF:

0.00243

AC:

488

AN:

201108

Hom.:

102

AF XY:

0.00180

AC XY:

195

AN XY:

108290

show subpopulations

Gnomad AFR exome

AF:

0.0286

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000984

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000694

Gnomad OTH exome

AF:

0.000191

GnomAD4 exome

AF:

0.000775

AC:

972

AN:

1253966

Hom.:

229

Cov.:

AF XY:

0.000687

AC XY:

426

AN XY:

620410

show subpopulations

Gnomad4 AFR exome

AF:

0.0252

Gnomad4 AMR exome

AF:

0.00158

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000338

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000442

Gnomad4 OTH exome

AF:

0.00180

GnomAD4 genome

AF:

0.00785

AC:

995

AN:

126722

Hom.:

188

Cov.:

AF XY:

0.00778

AC XY:

471

AN XY:

60520

show subpopulations

Gnomad4 AFR

AF:

0.0259

Gnomad4 AMR

AF:

0.00178

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000352

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000335

Gnomad4 OTH

AF:

0.00400

ESP6500AA

AF:

0.0328

AC:

137

ESP6500EA

AF:

0.000127

AC:

ExAC

AF:

0.00296

AC:

310

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

UGT2B17-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0020

DANN

Benign

0.13

DEOGEN2

Benign

0.021

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.035

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.86

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

0.30

REVEL

Benign

0.019

Sift

Benign

1.0

Sift4G

Benign

0.49

Vest4

0.069

MVP

0.14

MPC

0.073

ClinPred

0.0098

GERP RS

-5.3

Varity_R

0.018

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over