Variant 4-69212703-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001073.3(UGT2B11):c.740T>C(p.Phe247Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000726 in 151,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UGT2B11
NM_001073.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.26

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03213629).

BP6

Variant 4-69212703-A-G is Benign according to our data. Variant chr4-69212703-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3330860.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B11	NM_001073.3 linkuse as main transcript	c.740T>C	p.Phe247Ser	missense_variant	2/6	ENST00000446444.2	NP_001064.1
LOC105377267	NR_136191.1 linkuse as main transcript	n.679+1556A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
UGT2B11	ENST00000446444.2 linkuse as main transcript	c.740T>C	p.Phe247Ser	missense_variant	2/6	1	NM_001073.3	ENSP00000387683	P1
	ENST00000504301.5 linkuse as main transcript	n.566+1556A>G		intron_variant, non_coding_transcript_variant		5
	ENST00000505646.1 linkuse as main transcript	n.354+1556A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000726

AC:

AN:

151614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248188

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134208

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000549

AC:

AN:

1457404

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

724896

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000726

AC:

AN:

151614

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

74026

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000127

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0010

DANN

Benign

0.47

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.093

M_CAP

Benign

0.0027

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.63

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.93

REVEL

Benign

0.056

Sift

Benign

0.49

Sift4G

Benign

0.71

Polyphen

0.0

Vest4

0.12

MVP

0.18

MPC

0.0095

ClinPred

0.023

GERP RS

-3.9

Varity_R

0.062

gMVP

0.18

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