Variant 1-248650469-T-C 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_001001824.2(OR2T27):c.416A>G(p.Lys139Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000573 in 1,431,148 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000057 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

OR2T27
NM_001001824.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.90

Variant links:

Genes affected

OR2T27 (HGNC:31252): (olfactory receptor family 2 subfamily T member 27) 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]

OR2T27 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=0.02546689).

BP6

Variant 1-248650469-T-C is Benign according to our data. Variant chr1-248650469-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3302766.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T27	NM_001001824.2 linkuse as main transcript	c.416A>G	p.Lys139Arg	missense_variant	2/2	ENST00000460972.4
OR2T27	NM_001386060.1 linkuse as main transcript	c.416A>G	p.Lys139Arg	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T27	ENST00000460972.4 linkuse as main transcript	c.416A>G	p.Lys139Arg	missense_variant	2/2		NM_001001824.2	P1
OR2T27	ENST00000641652.1 linkuse as main transcript	c.416A>G	p.Lys139Arg	missense_variant	3/3			P1

Frequencies

GnomAD3 genomes

AF:

0.000159

AC:

AN:

126132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00128

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:

0.0000541

Gnomad OTH

AF:

0.00120

GnomAD3 exomes

AF:

0.000114

AC:

AN:

245448

Hom.:

AF XY:

0.000143

AC XY:

AN XY:

132672

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000741

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:

0.0000180

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000573

AC:

AN:

1431148

Hom.:

Cov.:

AF XY:

0.0000590

AC XY:

AN XY:

712180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000663

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000331

Gnomad4 OTH exome

AF:

0.000270

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000159

AC:

AN:

126132

Hom.:

Cov.:

AF XY:

0.000251

AC XY:

AN XY:

59870

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00128

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000541

Gnomad4 OTH

AF:

0.00120

Alfa

AF:

0.000169

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000417

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

Mar 31, 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

0.061

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.14

DANN

Benign

0.13

DEOGEN2

Benign

0.00046

T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.043

.;.;T

M_CAP

Benign

0.00098

MetaRNN

Benign

0.025

T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

1.1

.;.;N

REVEL

Benign

0.0070

Sift

Benign

1.0

.;.;T

Sift4G

Benign

1.0

.;.;T

Polyphen

0.0

B;B;B

Vest4

0.042

MVP

0.19

MPC

0.40

ClinPred

0.028

GERP RS

-2.5

Varity_R

0.028

gMVP

0.064

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