Variant 1-248273336-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001004695.2(OR2T33):c.479T>C(p.Val160Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 17 hom., cov: 33)

Exomes 𝑓: 0.24 ( 66 hom. )

Failed GnomAD Quality Control

Consequence

OR2T33
NM_001004695.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.73

Variant links:

Genes affected

OR2T33 (HGNC:31255): (olfactory receptor family 2 subfamily T member 33) 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]

OR2T33 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024973452).

BP6

Variant 1-248273336-A-G is Benign according to our data. Variant chr1-248273336-A-G is described in ClinVar as [Benign]. Clinvar id is 403272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T33	NM_001004695.2 linkuse as main transcript	c.479T>C	p.Val160Ala	missense_variant	2/2	ENST00000641220.1	NP_001004695.1	Q8NG76

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2T33	ENST00000641220.1 linkuse as main transcript	c.479T>C	p.Val160Ala	missense_variant	2/2		NM_001004695.2	ENSP00000493437.1		Q8NG76
OR2T33	ENST00000318021.4 linkuse as main transcript	c.479T>C	p.Val160Ala	missense_variant	1/1	6		ENSP00000324687.2		Q8NG76

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

4268

AN:

110592

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0554

Gnomad AMI

AF:

0.0111

Gnomad AMR

AF:

0.0322

Gnomad ASJ

AF:

0.0261

Gnomad EAS

AF:

0.00915

Gnomad SAS

AF:

0.0245

Gnomad FIN

AF:

0.0413

Gnomad MID

AF:

0.0340

Gnomad NFE

AF:

0.0331

Gnomad OTH

AF:

0.0414

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.244

AC:

211383

AN:

865754

Hom.:

Cov.:

121

AF XY:

0.235

AC XY:

101799

AN XY:

432548

show subpopulations

Gnomad4 AFR exome

AF:

0.166

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.0289

Gnomad4 SAS exome

AF:

0.0849

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0387

AC:

4279

AN:

110664

Hom.:

Cov.:

AF XY:

0.0408

AC XY:

2202

AN XY:

53960

show subpopulations

Gnomad4 AFR

AF:

0.0555

Gnomad4 AMR

AF:

0.0322

Gnomad4 ASJ

AF:

0.0261

Gnomad4 EAS

AF:

0.00919

Gnomad4 SAS

AF:

0.0248

Gnomad4 FIN

AF:

0.0413

Gnomad4 NFE

AF:

0.0331

Gnomad4 OTH

AF:

0.0410

Alfa

AF:

0.180

Hom.:

ExAC

AF:

0.388

AC:

47132

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.35

DANN

Benign

0.22

DEOGEN2

Benign

0.0066

T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.0016

.;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.33

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.020

.;N

REVEL

Benign

0.017

Sift

Benign

1.0

.;T

Sift4G

Benign

0.48

.;T

Polyphen

0.0

B;B

Vest4

0.056

MPC

1.3

ClinPred

0.0030

GERP RS

-2.8

Varity_R

0.037

gMVP

0.13

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

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