Genetic Variant ENST00000641896.1:c.454A>G (chr11-4587344-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000641896.1(OR52I2):c.454A>G(p.Ile152Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,458,716 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 59 hom. )

Failed GnomAD Quality Control

Consequence

OR52I2
ENST00000641896.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.531

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067687333).

BP6

Variant 11-4587344-A-G is Benign according to our data. Variant chr11-4587344-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2641532.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 59 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641896.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52I2	NM_001405760.1	MANE Select	c.454A>G	p.Ile152Val	missense	Exon 2 of 2	NP_001392689.1	A0A126GWK8
	OR52I2	NM_001005170.4		c.454A>G	p.Ile152Val	missense	Exon 1 of 1	NP_001005170.2	A0A126GWK8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52I2	ENST00000641896.1	MANE Select	c.454A>G	p.Ile152Val	missense	Exon 2 of 2	ENSP00000493402.1	A0A126GWK8
	OR52I2	ENST00000641486.1		c.454A>G	p.Ile152Val	missense	Exon 1 of 1	ENSP00000493314.1	A0A126GWK8

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

161

AN:

148258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00368

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000993

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000484

GnomAD2 exomes

AF:

0.000343

AC:

AN:

250694

AF XY:

0.000339

show subpopulations

Gnomad AFR exome

AF:

0.00343

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000186

AC:

271

AN:

1458716

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

135

AN XY:

725896

show subpopulations

African (AFR)

AF:

0.00480

AC:

149

AN:

31026

American (AMR)

AF:

0.000269

AC:

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26092

East Asian (EAS)

AF:

0.000454

AC:

AN:

39684

South Asian (SAS)

AF:

0.000649

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0000225

AC:

AN:

1111808

Other (OTH)

AF:

0.000133

AC:

AN:

60110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00109

AC:

161

AN:

148370

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

72660

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00367

AC:

139

AN:

37846

American (AMR)

AF:

0.000992

AC:

AN:

15122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.000479

AC:

AN:

2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.340

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00254

Hom.:

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000816

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.00066

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.48

M_CAP

Benign

0.0084

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.86

MutationAssessor

Benign

-0.41

PhyloP100

-0.53

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.12

REVEL

Benign

0.16

Sift

Benign

0.44

Sift4G

Benign

0.58

Polyphen

0.83

Vest4

0.055

MVP

0.54

MPC

0.18

ClinPred

0.035

GERP RS

1.9

Varity_R

0.037

gMVP

0.19

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over