dbSNP rs1770043: OR2T5:p.Lys13Arg (chr1-248488626-A-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

15 publications found

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:

ENSG00000229255 (HGNC:):

ENSG00000229255 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 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 VariationId is 403273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 426646 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004697.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T5	NM_001004697.2	MANE Select	c.38A>G	p.Lys13Arg	missense	Exon 1 of 1	NP_001004697.1	Q6IEZ7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR2T5	ENST00000641363.1	MANE Select	c.38A>G	p.Lys13Arg	missense	Exon 1 of 1	ENSP00000493066.1	Q6IEZ7
ENSG00000229255	ENST00000450847.2	TSL:2	n.279-3142T>C		intron	N/A
ENSG00000229255	ENST00000825060.1		n.326-3142T>C		intron	N/A

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

GnomAD2 exomes

AF:

0.711

AC:

80058

AN:

112530

AF XY:

0.703

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.961

AC:

18096

AN:

18824

American (AMR)

AF:

0.908

AC:

31085

AN:

34218

Ashkenazi Jewish (ASJ)

AF:

0.925

AC:

19225

AN:

20778

East Asian (EAS)

AF:

1.00

AC:

35132

AN:

35148

South Asian (SAS)

AF:

0.960

AC:

68835

AN:

71680

European-Finnish (FIN)

AF:

0.792

AC:

32691

AN:

41266

Middle Eastern (MID)

AF:

0.933

AC:

4555

AN:

4884

European-Non Finnish (NFE)

AF:

0.845

AC:

700359

AN:

828746

Other (OTH)

AF:

0.882

AC:

40146

AN:

45510

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.270

Heterozygous variant carriers

9841

19682

29522

39363

49204

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15546

31092

46638

62184

77730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.628

AC:

2116

AN:

3372

American (AMR)

AF:

0.707

AC:

3647

AN:

5158

Ashkenazi Jewish (ASJ)

AF:

0.808

AC:

1162

AN:

1438

East Asian (EAS)

AF:

0.998

AC:

1267

AN:

1270

South Asian (SAS)

AF:

0.802

AC:

597

AN:

744

European-Finnish (FIN)

AF:

0.504

AC:

2015

AN:

3996

Middle Eastern (MID)

AF:

0.740

AC:

AN:

European-Non Finnish (NFE)

AF:

0.686

AC:

20327

AN:

29638

Other (OTH)

AF:

0.678

AC:

457

AN:

674

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.316

Heterozygous variant carriers

440

881

1321

1762

2202

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.744

Hom.:

3329

ExAC

AF:

0.736

AC:

80646

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.0

(source)

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

PhyloP100

-1.2

PrimateAI

Benign

0.19

Polyphen

0.0

ClinPred

0.0051

GERP RS

-1.3

PromoterAI

0.015

Neutral

(source)

Varity_R

0.032

gMVP

0.045

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over