dbSNP rs143304000: UGT2B11:p.Ala346Val (chr4-69205533-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001073.3(UGT2B11):c.1037C>T(p.Ala346Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000392 in 1,610,484 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.0019 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

UGT2B11
NM_001073.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.927

Variant links:

Genes affected

UGT2B11 (HGNC:12545): (UDP glucuronosyltransferase family 2 member B11) Enables glucuronosyltransferase activity. Involved in estrogen metabolic process and xenobiotic glucuronidation. 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]

UGT2B11 links:

ENSG00000250696 (HGNC:):

ENSG00000250696 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0149798095).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B11	NM_001073.3 link	c.1037C>T	p.Ala346Val	missense_variant	Exon 4 of 6	ENST00000446444.2	NP_001064.1	O75310

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UGT2B11	ENST00000446444.2 link	c.1037C>T	p.Ala346Val	missense_variant	Exon 4 of 6	1	NM_001073.3	ENSP00000387683.1	O75310
UGT2B11	ENST00000513315.1 link	n.161C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3
ENSG00000250696	ENST00000504301.5 link	n.484+4955G>A		intron_variant	Intron 3 of 4	5
ENSG00000250696	ENST00000505646.1 link	n.272+4249G>A		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

279

AN:

151648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00658

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000551

AC:

138

AN:

250514

Hom.:

AF XY:

0.000369

AC XY:

AN XY:

135430

show subpopulations

Gnomad AFR exome

AF:

0.00748

Gnomad AMR exome

AF:

0.000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000239

AC:

348

AN:

1458718

Hom.:

Cov.:

AF XY:

0.000197

AC XY:

143

AN XY:

725784

show subpopulations

Gnomad4 AFR exome

AF:

0.00800

Gnomad4 AMR exome

AF:

0.000404

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000901

Gnomad4 OTH exome

AF:

0.000814

GnomAD4 genome

AF:

0.00186

AC:

283

AN:

151766

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

157

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.00665

Gnomad4 AMR

AF:

0.0000658

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000391

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000255

Hom.:

Bravo

AF:

0.00230

ESP6500AA

AF:

0.00840

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000634

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0026

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.76

M_CAP

Benign

0.0092

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.040

REVEL

Benign

0.098

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.15

Vest4

0.25

MVP

0.34

MPC

0.010

ClinPred

0.019

GERP RS

-0.15

Varity_R

0.13

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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