1-248488626-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001004697.2(OR2T5):c.38A>G(p.Lys13Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.68 ( 12178 hom., cov: 7)

Exomes 𝑓: 0.86 ( 426646 hom. )

Failed GnomAD Quality Control

Consequence

OR2T5
NM_001004697.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.17

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.0693344E-6).

BP6

Variant 1-248488626-A-G is Benign according to our data. Variant chr1-248488626-A-G is described in ClinVar as [Benign]. Clinvar id is 403273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T5	NM_001004697.2 link	c.38A>G	p.Lys13Arg	missense_variant	Exon 1 of 1	ENST00000641363.1	NP_001004697.1	Q6IEZ7
LOC105373277	XR_001738575.2 link	n.144-3142T>C		intron_variant	Intron 2 of 2
LOC105373277	XR_002958498.2 link	n.188-3142T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2T5	ENST00000641363.1 link	c.38A>G	p.Lys13Arg	missense_variant	Exon 1 of 1		NM_001004697.2	ENSP00000493066.1		Q6IEZ7

Frequencies

GnomAD3 genomes

AF:

0.682

AC:

31906

AN:

46790

Hom.:

12165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.627

Gnomad AMI

AF:

0.648

Gnomad AMR

AF:

0.707

Gnomad ASJ

AF:

0.808

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.802

Gnomad FIN

AF:

0.504

Gnomad MID

AF:

0.740

Gnomad NFE

AF:

0.686

Gnomad OTH

AF:

0.674

GnomAD3 exomes

AF:

0.711

AC:

80058

AN:

112530

Hom.:

39156

AF XY:

0.703

AC XY:

41793

AN XY:

59416

show subpopulations

Gnomad AFR exome

AF:

0.874

Gnomad AMR exome

AF:

0.740

Gnomad ASJ exome

AF:

0.790

Gnomad EAS exome

AF:

0.997

Gnomad SAS exome

AF:

0.861

Gnomad FIN exome

AF:

0.624

Gnomad NFE exome

AF:

0.608

Gnomad OTH exome

AF:

0.718

GnomAD4 exome

AF:

0.863

AC:

950124

AN:

1101054

Hom.:

426646

Cov.:

AF XY:

0.867

AC XY:

480448

AN XY:

554254

show subpopulations

Gnomad4 AFR exome

AF:

0.961

Gnomad4 AMR exome

AF:

0.908

Gnomad4 ASJ exome

AF:

0.925

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.960

Gnomad4 FIN exome

AF:

0.792

Gnomad4 NFE exome

AF:

0.845

Gnomad4 OTH exome

AF:

0.882

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.682

AC:

31931

AN:

46812

Hom.:

12178

Cov.:

AF XY:

0.683

AC XY:

15569

AN XY:

22792

show subpopulations

Gnomad4 AFR

AF:

0.628

Gnomad4 AMR

AF:

0.707

Gnomad4 ASJ

AF:

0.808

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.802

Gnomad4 FIN

AF:

0.504

Gnomad4 NFE

AF:

0.686

Gnomad4 OTH

AF:

0.678

Alfa

AF:

0.744

Hom.:

3329

ExAC

AF:

0.736

AC:

80646

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.0

DANN

Benign

0.80

DEOGEN2

Benign

0.0021

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00092

MetaRNN

Benign

0.0000021

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.97

PrimateAI

Benign

0.19

Polyphen

0.0

ClinPred

0.0051

GERP RS

-1.3

Varity_R

0.032

gMVP

0.045

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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