Variant chr1-248489049-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001004697.2(OR2T5):c.461T>C(p.Phe154Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.057 ( 0 hom., cov: 0)

Exomes 𝑓: 0.13 ( 466 hom. )

Failed GnomAD Quality Control

Consequence

OR2T5
NM_001004697.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.521

Variant links:

Genes affected

OR2T5 (HGNC:15017): (olfactory receptor family 2 subfamily T member 5) 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]

OR2T5 links:

LOC105373277 (HGNC:):

LOC105373277 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063756704).

BP6

Variant 1-248489049-T-C is Benign according to our data. Variant chr1-248489049-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2213065.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR2T5	NM_001004697.2 linkuse as main transcript	c.461T>C	p.Phe154Ser	missense_variant	1/1	ENST00000641363.1
LOC105373277	XR_002958498.2 linkuse as main transcript	n.188-3565A>G		intron_variant, non_coding_transcript_variant
LOC105373277	XR_001738575.2 linkuse as main transcript	n.144-3565A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T5	ENST00000641363.1 linkuse as main transcript	c.461T>C	p.Phe154Ser	missense_variant	1/1		NM_001004697.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

520

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0606

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.300

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0714

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0435

Gnomad OTH

AF:

0.0833

GnomAD3 exomes

AF:

0.186

AC:

7774

AN:

41840

Hom.:

AF XY:

0.185

AC XY:

3897

AN XY:

21074

show subpopulations

Gnomad AFR exome

AF:

0.296

Gnomad AMR exome

AF:

0.169

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.343

Gnomad SAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.0958

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.135

AC:

39331

AN:

291366

Hom.:

466

Cov.:

AF XY:

0.140

AC XY:

21447

AN XY:

153208

show subpopulations

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.292

Gnomad4 SAS exome

AF:

0.241

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.0954

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0573

AC:

AN:

524

Hom.:

Cov.:

AF XY:

0.0789

AC XY:

AN XY:

266

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0588

Gnomad4 ASJ

AF:

0.214

Gnomad4 EAS

AF:

0.300

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.0714

Gnomad4 NFE

AF:

0.0435

Gnomad4 OTH

AF:

0.0714

Alfa

AF:

0.125

Hom.:

ExAC

AF:

0.0180

AC:

154

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 22, 2022

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

0.16

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.026

MetaRNN

Benign

0.0064

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

Polyphen

0.73

ClinPred

0.051

GERP RS

2.6

Varity_R

0.39

gMVP

0.17

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