14-19936123-G-A

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001004063.3(OR4K1):c.457G>A(p.Val153Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,613,860 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V153F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 36)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

OR4K1
NM_001004063.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.186

Variant links:

Genes affected

OR4K1 (HGNC:14726): (olfactory receptor family 4 subfamily K 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]

OR4K1 links:

LOC124903278 (HGNC:):

LOC124903278 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007221937).

BP6

Variant 14-19936123-G-A is Benign according to our data. Variant chr14-19936123-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2204203.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4K1	NM_001004063.3 link	c.457G>A	p.Val153Ile	missense_variant	Exon 2 of 2	ENST00000641172.1	NP_001004063.2	Q8NGD4
OR4K1	XM_011537153.3 link	c.457G>A	p.Val153Ile	missense_variant	Exon 3 of 3		XP_011535455.1	Q8NGD4
LOC124903278	XR_007064055.1 link	n.165+7602C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR4K1	ENST00000641172.1 link	c.457G>A	p.Val153Ile	missense_variant	Exon 2 of 2		NM_001004063.3	ENSP00000493193.1	Q8NGD4
OR4K1	ENST00000285600.4 link	c.457G>A	p.Val153Ile	missense_variant	Exon 1 of 1	6		ENSP00000285600.3	Q8NGD4
OR4K1	ENST00000641429.1 link	c.457G>A	p.Val153Ile	missense_variant	Exon 3 of 3			ENSP00000493205.1	Q8NGD4

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000263

AC:

AN:

251220

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000177

AC:

258

AN:

1461700

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

133

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00264

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000283

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000459

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000336

Hom.:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000329

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 10, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.00077

T;T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.22

.;.;T

M_CAP

Benign

0.00099

MetaRNN

Benign

0.0072

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.60

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

0.77

.;.;N

REVEL

Benign

0.031

Sift

Benign

0.50

.;.;T

Sift4G

Benign

0.20

.;.;T

Polyphen

0.0010

B;B;B

Vest4

0.055

MVP

0.11

MPC

0.0011

ClinPred

0.0035

GERP RS

2.3

Varity_R

0.034

gMVP

0.052

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