Variant 4-69480847-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021139.3(UGT2B4):c.1374T>A(p.Asp458Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,560 control chromosomes in the GnomAD database, including 44,666 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3267 hom., cov: 31)

Exomes 𝑓: 0.23 ( 41399 hom. )

Consequence

UGT2B4
NM_021139.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.933

Variant links:

Genes affected

UGT2B4 (HGNC:12553): (UDP glucuronosyltransferase family 2 member B4) Enables glucuronosyltransferase activity. Involved in cellular glucuronidation and estrogen metabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

UGT2B4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009637177).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B4	NM_021139.3 link	c.1374T>A	p.Asp458Glu	missense_variant	6/6	ENST00000305107.7	NP_066962.2	P06133-1
UGT2B4	NM_001297616.2 link	c.966T>A	p.Asp322Glu	missense_variant	7/7		NP_001284545.1	P06133-2
UGT2B4	NM_001297615.2 link	c.*44T>A		3_prime_UTR_variant	5/5		NP_001284544.1	P06133-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UGT2B4	ENST00000305107.7 link	c.1374T>A	p.Asp458Glu	missense_variant	6/6	1	NM_021139.3	ENSP00000305221.6	P06133-1
UGT2B4	ENST00000512583 link	c.*44T>A		3_prime_UTR_variant	5/5	1		ENSP00000421290.1	P06133-3
UGT2B4	ENST00000506580.5 link	n.936T>A		non_coding_transcript_exon_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30353

AN:

151846

Hom.:

3262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.0952

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.196

GnomAD3 exomes

AF:

0.199

AC:

50090

AN:

251082

Hom.:

5956

AF XY:

0.194

AC XY:

26370

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.290

Gnomad ASJ exome

AF:

0.166

Gnomad EAS exome

AF:

0.000870

Gnomad SAS exome

AF:

0.0930

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.229

AC:

335067

AN:

1461596

Hom.:

41399

Cov.:

AF XY:

0.224

AC XY:

163220

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.284

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.0951

Gnomad4 FIN exome

AF:

0.212

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.200

AC:

30380

AN:

151964

Hom.:

3267

Cov.:

AF XY:

0.195

AC XY:

14481

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.229

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.0949

Gnomad4 FIN

AF:

0.212

Gnomad4 NFE

AF:

0.246

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.192

Hom.:

1021

Bravo

AF:

0.201

TwinsUK

AF:

0.268

AC:

994

ALSPAC

AF:

0.257

AC:

989

ESP6500AA

AF:

0.143

AC:

628

ESP6500EA

AF:

0.238

AC:

2045

ExAC

AF:

0.193

AC:

23467

Asia WGS

AF:

0.0830

AC:

289

AN:

3476

EpiCase

AF:

0.236

EpiControl

AF:

0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.24

Sift

Uncertain

0.023

Sift4G

Uncertain

0.024

Polyphen

0.39

Vest4

0.062

MutPred

0.29

Loss of helix (P = 0.0167);

MPC

0.077

ClinPred

0.091

GERP RS

-3.8

Varity_R

0.31

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over