1-247921459-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001005522.2(OR2T8):c.442C>T(p.Leu148Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 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: 5)

Exomes 𝑓: 0.000067 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

OR2T8
NM_001005522.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -8.75

Publications

2 publications found

Variant links:

Genes affected

OR2T8 (HGNC:15020): (olfactory receptor family 2 subfamily T member 8) 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]

OR2T8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013972938).

BP6

Variant 1-247921459-C-T is Benign according to our data. Variant chr1-247921459-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2396839.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T8	NM_001005522.2 link	c.442C>T	p.Leu148Phe	missense_variant	Exon 2 of 2	ENST00000641945.2	NP_001005522.1	A6NH00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2T8	ENST00000641945.2 link	c.442C>T	p.Leu148Phe	missense_variant	Exon 2 of 2		NM_001005522.2	ENSP00000493286.1		A6NH00

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

27476

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000141

AC:

AN:

183974

AF XY:

0.000121

show subpopulations

Gnomad AFR exome

AF:

0.000893

Gnomad AMR exome

AF:

0.0000715

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000119

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000669

AC:

AN:

1061216

Hom.:

Cov.:

AF XY:

0.0000696

AC XY:

AN XY:

531606

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25164

American (AMR)

AF:

0.00

AC:

AN:

32834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20610

East Asian (EAS)

AF:

0.00208

AC:

AN:

31788

South Asian (SAS)

AF:

0.00

AC:

AN:

57770

European-Finnish (FIN)

AF:

0.0000243

AC:

AN:

41224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3208

European-Non Finnish (NFE)

AF:

0.00000498

AC:

AN:

802608

Other (OTH)

AF:

0.00

AC:

AN:

46010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

27476

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11602

African (AFR)

AF:

0.00

AC:

AN:

8990

American (AMR)

AF:

0.00

AC:

AN:

2018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

684

East Asian (EAS)

AF:

0.00

AC:

AN:

908

South Asian (SAS)

AF:

0.00

AC:

AN:

666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

152

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

12434

Other (OTH)

AF:

0.00

AC:

AN:

376

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 09, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

0.098

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.019

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.0075

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.094

.;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.23

N;N

PhyloP100

-8.7

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.97

.;N

REVEL

Benign

0.014

Sift

Benign

0.93

.;T

Sift4G

Benign

0.72

.;T

Polyphen

0.0080

B;B

Vest4

0.033

MutPred

0.35

Gain of catalytic residue at L148 (P = 0.0705);Gain of catalytic residue at L148 (P = 0.0705);

MVP

0.41

ClinPred

0.029

GERP RS

-6.8

Varity_R

0.058

gMVP

0.076

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-247921459-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over