Variant 1-247757635-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_012353.3(OR1C1):c.772G>A(p.Val258Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000929 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

OR1C1
NM_012353.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.22

Variant links:

Genes affected

OR1C1 (HGNC:8182): (olfactory receptor family 1 subfamily C 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]

OR1C1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07833728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR1C1	NM_012353.3 linkuse as main transcript	c.772G>A	p.Val258Ile	missense_variant	2/2	ENST00000641256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR1C1	ENST00000641256.1 linkuse as main transcript	c.772G>A	p.Val258Ile	missense_variant	2/2		NM_012353.3	P1
	ENST00000662798.1 linkuse as main transcript	n.768C>T		non_coding_transcript_exon_variant	2/4

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000100

AC:

AN:

249120

Hom.:

AF XY:

0.000126

AC XY:

AN XY:

135146

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000334

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000797

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000944

AC:

138

AN:

1461818

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000908

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.0000661

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Mar 18, 2024

The c.772G>A (p.V258I) alteration is located in exon 1 (coding exon 1) of the OR1C1 gene. This alteration results from a G to A substitution at nucleotide position 772, causing the valine (V) at amino acid position 258 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

0.10

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0043

T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.53

.;N

REVEL

Benign

0.060

Sift

Benign

0.064

.;T

Sift4G

Uncertain

0.054

.;T

Polyphen

0.85

P;P

Vest4

0.058

MVP

0.19

MPC

0.020

ClinPred

0.11

GERP RS

3.2

Varity_R

0.048

gMVP

0.022

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

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