dbSNP rs751720185: OR2T8:p.Leu148Ile (chr1-247921459-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005522.2(OR2T8):c.442C>A(p.Leu148Ile) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L148F) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 5)

Exomes 𝑓: 0.00017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR2T8
NM_001005522.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014972806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2T8	NM_001005522.2 link	c.442C>A	p.Leu148Ile	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>A	p.Leu148Ile	missense_variant	Exon 2 of 2		NM_001005522.2	ENSP00000493286.1		A6NH00

Frequencies

GnomAD3 genomes

AF:

0.000146

AC:

AN:

27464

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000496

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00110

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000804

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000598

AC:

AN:

183974

AF XY:

0.0000506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000715

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000158

Gnomad FIN exome

AF:

0.0000626

Gnomad NFE exome

AF:

0.0000477

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000165

AC:

175

AN:

1059704

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

AN XY:

530806

show subpopulations

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

African (AFR)

AF:

0.0000796

AC:

AN:

25138

American (AMR)

AF:

0.000305

AC:

AN:

32792

Ashkenazi Jewish (ASJ)

AF:

0.0000486

AC:

AN:

20576

East Asian (EAS)

AF:

0.000536

AC:

AN:

31736

South Asian (SAS)

AF:

0.000747

AC:

AN:

57578

European-Finnish (FIN)

AF:

0.0000973

AC:

AN:

41126

Middle Eastern (MID)

AF:

0.000313

AC:

AN:

3198

European-Non Finnish (NFE)

AF:

0.000115

AC:

AN:

801620

Other (OTH)

AF:

0.000109

AC:

AN:

45940

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.304

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: AS_VQSR

AF:

0.000146

AC:

AN:

27472

Hom.:

Cov.:

AF XY:

0.0000860

AC XY:

AN XY:

11622

show subpopulations

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

African (AFR)

AF:

0.000111

AC:

AN:

9030

American (AMR)

AF:

0.000496

AC:

AN:

2016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

684

East Asian (EAS)

AF:

0.00111

AC:

AN:

900

South Asian (SAS)

AF:

0.00

AC:

AN:

654

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

140

European-Non Finnish (NFE)

AF:

0.0000805

AC:

AN:

12424

Other (OTH)

AF:

0.00

AC:

AN:

378

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.238

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.0000444

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.0070

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.0036

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.088

.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.20

N;N

PhyloP100

-8.7

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.40

.;N

REVEL

Benign

0.015

Sift

Benign

0.76

.;T

Sift4G

Benign

0.97

.;T

Polyphen

0.020

B;B

Vest4

0.076

MutPred

0.28

Gain of MoRF binding (P = 0.3541);Gain of MoRF binding (P = 0.3541);

MVP

0.39

ClinPred

0.083

GERP RS

-6.8

Varity_R

0.094

gMVP

0.033

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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rs751720185

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over