Variant 1-248294821-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001004692.2(OR2T12):c.758G>C(p.Gly253Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,613,010 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00097 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0011 ( 4 hom. )

Consequence

OR2T12
NM_001004692.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.00

Variant links:

Genes affected

OR2T12 (HGNC:19592): (olfactory receptor family 2 subfamily T member 12) 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]

OR2T12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011195511).

BP6

Variant 1-248294821-C-G is Benign according to our data. Variant chr1-248294821-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2280874.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T12	NM_001004692.2 linkuse as main transcript	c.758G>C	p.Gly253Ala	missense_variant	3/3	ENST00000641276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T12	ENST00000641276.1 linkuse as main transcript	c.758G>C	p.Gly253Ala	missense_variant	3/3		NM_001004692.2	P1

Frequencies

GnomAD3 genomes

AF:

0.000968

AC:

147

AN:

151868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000823

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000844

AC:

212

AN:

251142

Hom.:

AF XY:

0.000847

AC XY:

115

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.00112

AC:

1639

AN:

1461036

Hom.:

Cov.:

101

AF XY:

0.00109

AC XY:

789

AN XY:

726876

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.000510

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00128

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.000974

AC:

148

AN:

151974

Hom.:

Cov.:

AF XY:

0.000889

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.000845

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000574

Hom.:

Bravo

AF:

0.00110

ExAC

AF:

0.000898

AC:

109

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

Aug 30, 2021

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

0.064

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.14

DANN

Benign

0.061

DEOGEN2

Benign

0.00032

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.17

.;T

M_CAP

Benign

0.00063

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.3

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

3.2

.;N

REVEL

Benign

0.052

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.0

B;B

Vest4

0.050

MVP

0.11

MPC

0.48

ClinPred

0.011

GERP RS

0.23

Varity_R

0.031

gMVP

0.065

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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