Variant chr1-247896121-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001001957.2(OR2W3):c.535C>T(p.Arg179Cys) variant causes a missense change. The variant allele was found at a frequency of 0.507 in 1,613,738 control chromosomes in the GnomAD database, including 213,360 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R179H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.43 ( 15702 hom., cov: 33)

Exomes 𝑓: 0.52 ( 197658 hom. )

Consequence

OR2W3
NM_001001957.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.59

Variant links:

Genes affected

OR2W3 (HGNC:15021): (olfactory receptor family 2 subfamily W member 3) 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]

OR2W3 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=3.8534534E-5).

BP6

Variant 1-247896121-C-T is Benign according to our data. Variant chr1-247896121-C-T is described in ClinVar as [Benign]. Clinvar id is 1582338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2W3	NM_001001957.2 link	c.535C>T	p.Arg179Cys	missense_variant	1/1	ENST00000360358.3	NP_001001957.2	Q7Z3T1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2W3	ENST00000360358.3 link	c.535C>T	p.Arg179Cys	missense_variant	1/1	6	NM_001001957.2	ENSP00000353516.3		Q7Z3T1

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65665

AN:

151958

Hom.:

15702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.494

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.444

GnomAD3 exomes

AF:

0.480

AC:

120564

AN:

251182

Hom.:

30348

AF XY:

0.486

AC XY:

65922

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.511

Gnomad EAS exome

AF:

0.564

Gnomad SAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.536

Gnomad OTH exome

AF:

0.495

GnomAD4 exome

AF:

0.515

AC:

753060

AN:

1461662

Hom.:

197658

Cov.:

AF XY:

0.513

AC XY:

373340

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.355

Gnomad4 ASJ exome

AF:

0.511

Gnomad4 EAS exome

AF:

0.508

Gnomad4 SAS exome

AF:

0.419

Gnomad4 FIN exome

AF:

0.573

Gnomad4 NFE exome

AF:

0.537

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.432

AC:

65672

AN:

152076

Hom.:

15702

Cov.:

AF XY:

0.431

AC XY:

32079

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.225

Gnomad4 AMR

AF:

0.381

Gnomad4 ASJ

AF:

0.510

Gnomad4 EAS

AF:

0.560

Gnomad4 SAS

AF:

0.422

Gnomad4 FIN

AF:

0.572

Gnomad4 NFE

AF:

0.533

Gnomad4 OTH

AF:

0.445

Alfa

AF:

0.513

Hom.:

50557

Bravo

AF:

0.411

TwinsUK

AF:

0.545

AC:

2021

ALSPAC

AF:

0.540

AC:

2081

ESP6500AA

AF:

0.231

AC:

1016

ESP6500EA

AF:

0.532

AC:

4576

ExAC

AF:

0.477

AC:

57943

Asia WGS

AF:

0.482

AC:

1678

AN:

3478

EpiCase

AF:

0.538

EpiControl

AF:

0.531

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.13

DEOGEN2

Benign

0.0050

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.69

MetaRNN

Benign

0.000039

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-4.2

PrimateAI

Benign

0.39

PROVEAN

Benign

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.066

ClinPred

0.018

GERP RS

4.2

Varity_R

0.048

gMVP

0.12

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