1-248558785-T-G

Position:

chr1-248558785-T-G

Variant summary

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

The NM_001004694.3(OR2T29):c.707A>C(p.Glu236Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.35 ( 1196 hom. )

Failed GnomAD Quality Control

Consequence

OR2T29
NM_001004694.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.352

Variant links:

Genes affected

OR2T29 (HGNC:31253): (olfactory receptor family 2 subfamily T member 29) 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]

OR2T29 links:

ENSG00000224521 (HGNC:):

ENSG00000224521 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=0.0053547025).

BP6

Variant 1-248558785-T-G is Benign according to our data. Variant chr1-248558785-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2286946.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2T29	NM_001004694.3 linkuse as main transcript	c.707A>C	p.Glu236Ala	missense_variant	2/2	ENST00000641069.1	NP_001004694.2	Q8NH02

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OR2T29	ENST00000641069.1 linkuse as main transcript	c.707A>C	p.Glu236Ala	missense_variant	2/2		NM_001004694.3	ENSP00000492895.1	Q8NH02
OR2T29	ENST00000328570.6 linkuse as main transcript	c.707A>C	p.Glu236Ala	missense_variant	1/1	6		ENSP00000331774.3	Q8NH02
ENSG00000224521	ENST00000438623.1 linkuse as main transcript	n.92-3815T>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

Hom.:

Cov.:

FAILED QC

GnomAD3 exomes

AF:

0.391

AC:

2964

AN:

7590

Hom.:

496

AF XY:

0.389

AC XY:

1602

AN XY:

4118

show subpopulations

Gnomad AFR exome

AF:

0.325

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.641

Gnomad SAS exome

AF:

0.357

Gnomad FIN exome

AF:

0.476

Gnomad NFE exome

AF:

0.397

Gnomad OTH exome

AF:

0.301

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.351

AC:

10540

AN:

30018

Hom.:

1196

Cov.:

AF XY:

0.353

AC XY:

5413

AN XY:

15346

show subpopulations

Gnomad4 AFR exome

AF:

0.366

Gnomad4 AMR exome

AF:

0.314

Gnomad4 ASJ exome

AF:

0.311

Gnomad4 EAS exome

AF:

0.528

Gnomad4 SAS exome

AF:

0.376

Gnomad4 FIN exome

AF:

0.416

Gnomad4 NFE exome

AF:

0.329

Gnomad4 OTH exome

AF:

0.350

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.450

Hom.:

ExAC

AF:

0.200

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

May 01, 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

0.086

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.45

.;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-4.9

.;D

REVEL

Benign

0.036

Sift

Benign

0.060

.;T

Sift4G

Uncertain

0.047

.;D

Polyphen

0.087

B;B

Vest4

0.070

MPC

3.1

ClinPred

0.043

GERP RS

0.10

Varity_R

0.30

gMVP

0.12

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