Variant 11-56360386-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005205.3(OR8J1):c.140C>T(p.Thr47Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

OR8J1
NM_001005205.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.497

Variant links:

Genes affected

OR8J1 (HGNC:14855): (olfactory receptor family 8 subfamily J member 1) 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]

OR8J1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031867594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR8J1	NM_001005205.3 linkuse as main transcript	c.140C>T	p.Thr47Ile	missense_variant	2/2	ENST00000533152.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
OR8J1	ENST00000533152.3 linkuse as main transcript	c.140C>T	p.Thr47Ile	missense_variant	2/2	NM_001005205.3	P1
OR8J1	ENST00000303039.3 linkuse as main transcript	c.140C>T	p.Thr47Ile	missense_variant	1/1		P1
OR8J1	ENST00000641406.1 linkuse as main transcript	n.129C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251356

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.140C>T (p.T47I) alteration is located in exon 1 (coding exon 1) of the OR8J1 gene. This alteration results from a C to T substitution at nucleotide position 140, causing the threonine (T) at amino acid position 47 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.4

DANN

Benign

0.70

DEOGEN2

Benign

0.0016

T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.45

N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

1.2

.;N

REVEL

Benign

0.040

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

.;T

Polyphen

0.050

B;B

Vest4

0.085

MutPred

0.46

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.17

MPC

0.012

ClinPred

0.041

GERP RS

2.1

Varity_R

0.067

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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