Genetic Variant OR4K1:p.Ser7Trp (chr14-19935686-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001004063.3(OR4K1):c.20C>G(p.Ser7Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000552 in 1,448,564 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S7L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 37)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

OR4K1
NM_001004063.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.86

Publications

7 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004063.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4K1	NM_001004063.3	MANE Select	c.20C>G	p.Ser7Trp	missense	Exon 2 of 2	NP_001004063.2	Q8NGD4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR4K1	ENST00000641172.1	MANE Select	c.20C>G	p.Ser7Trp	missense	Exon 2 of 2	ENSP00000493193.1	Q8NGD4
OR4K1	ENST00000285600.4	TSL:6	c.20C>G	p.Ser7Trp	missense	Exon 1 of 1	ENSP00000285600.3	Q8NGD4
OR4K1	ENST00000641429.1		c.20C>G	p.Ser7Trp	missense	Exon 3 of 3	ENSP00000493205.1	Q8NGD4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000415

AC:

AN:

241092

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000560

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000552

AC:

AN:

1448564

Hom.:

Cov.:

AF XY:

0.00000695

AC XY:

AN XY:

719734

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

32442

American (AMR)

AF:

0.00

AC:

AN:

41704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25588

East Asian (EAS)

AF:

0.000202

AC:

AN:

39574

South Asian (SAS)

AF:

0.00

AC:

AN:

83290

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107368

Other (OTH)

AF:

0.00

AC:

AN:

59812

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000149702), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.344

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.068

FATHMM_MKL

Benign

0.53

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0098

MetaRNN

Uncertain

0.51

MetaSVM

Uncertain

-0.013

MutationAssessor

Pathogenic

4.1

PhyloP100

3.9

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-6.3

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.55

MutPred

0.46

Loss of disorder (P = 5e-04)

MVP

0.71

MPC

0.0011

ClinPred

0.90

GERP RS

3.9

PromoterAI

-0.026

Neutral

(source)

Varity_R

0.50

gMVP

0.51

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over