ENST00000641896.1:c.476C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000641896.1(OR52I2):c.476C>T(p.Ala159Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000597 in 1,457,792 control chromosomes in the GnomAD database, including 33 homozygotes. 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A159S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00076 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 33 hom. )

Failed GnomAD Quality Control

Consequence

OR52I2
ENST00000641896.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.00200

Variant links:

Genes affected

OR52I2 (HGNC:15221): (olfactory receptor family 52 subfamily I member 2) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

OR52I2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01751253).

BP6

Variant 11-4587366-C-T is Benign according to our data. Variant chr11-4587366-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2344612.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR52I2	NM_001005170.4 link	c.476C>T	p.Ala159Val	missense_variant	Exon 1 of 1		NP_001005170.2	Q8NH67A0A126GWK8
OR52I2	NM_001405760.1 link	c.476C>T	p.Ala159Val	missense_variant	Exon 2 of 2		NP_001392689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR52I2	ENST00000641896.1 link	c.476C>T	p.Ala159Val	missense_variant	Exon 2 of 2			ENSP00000493402.1		A0A126GWK8
OR52I2	ENST00000641486.1 link	c.476C>T	p.Ala159Val	missense_variant	Exon 1 of 1			ENSP00000493314.1		A0A126GWK8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

112

AN:

147036

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00279

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000332

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00148

GnomAD3 exomes

AF:

0.0000717

AC:

AN:

251156

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.00112

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000597

AC:

AN:

1457792

Hom.:

Cov.:

AF XY:

0.0000524

AC XY:

AN XY:

725434

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000667

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000761

AC:

112

AN:

147144

Hom.:

Cov.:

AF XY:

0.000735

AC XY:

AN XY:

72080

show subpopulations

Gnomad4 AFR

AF:

0.00278

Gnomad4 AMR

AF:

0.000331

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00146

Alfa

AF:

0.000671

Hom.:

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.554C>T (p.A185V) alteration is located in exon 1 (coding exon 1) of the OR52I2 gene. This alteration results from a C to T substitution at nucleotide position 554, causing the alanine (A) at amino acid position 185 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OR52I2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.13

DANN

Benign

0.38

DEOGEN2

Benign

0.00027

.;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.37

.;T;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.018

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

.;.;N

PrimateAI

Benign

0.22

PROVEAN

Benign

1.2

.;.;N

REVEL

Benign

0.057

Sift

Benign

0.66

.;.;T

Sift4G

Benign

0.41

.;.;T

Polyphen

0.027

.;.;B

Vest4

0.033

MutPred

0.32

.;.;Loss of methylation at R181 (P = 0.3272);

MVP

0.42

MPC

0.18

ClinPred

0.0066

GERP RS

-2.9

Varity_R

0.024

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