Genetic Variant OR2T4:p.Ser14* (chr1-248361705-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001004696.2(OR2T4):c.41C>A(p.Ser14*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000718 in 1,253,540 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000025 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000053 ( 0 hom. )

Consequence

OR2T4
NM_001004696.2 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.82

Publications

2 publications found

Variant links:

Genes affected

OR2T4 (HGNC:15016): (olfactory receptor family 2 subfamily T member 4) 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]

OR2T4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004696.2. 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
	OR2T4	NM_001004696.2	MANE Select	c.41C>A	p.Ser14*	stop_gained	Exon 1 of 1	NP_001004696.2	A0A2C9F2M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T4	ENST00000366473.4	TSL:6 MANE Select	c.41C>A	p.Ser14*	stop_gained	Exon 1 of 1	ENSP00000355429.3	A0A2C9F2M9

Frequencies

GnomAD3 genomes

AF:

0.0000254

AC:

AN:

117904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000757

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000408

AC:

AN:

244830

AF XY:

0.00000755

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000528

AC:

AN:

1135636

Hom.:

Cov.:

AF XY:

0.00000717

AC XY:

AN XY:

558026

show subpopulations

African (AFR)

AF:

0.0000620

AC:

AN:

32250

American (AMR)

AF:

0.00

AC:

AN:

29152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21464

East Asian (EAS)

AF:

0.00

AC:

AN:

15896

South Asian (SAS)

AF:

0.0000802

AC:

AN:

49854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4494

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

900416

Other (OTH)

AF:

0.00

AC:

AN:

46170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

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

AF:

0.0000254

AC:

AN:

117904

Hom.:

Cov.:

AF XY:

0.0000176

AC XY:

AN XY:

56962

show subpopulations

African (AFR)

AF:

0.0000757

AC:

AN:

39616

American (AMR)

AF:

0.00

AC:

AN:

10120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2740

East Asian (EAS)

AF:

0.00

AC:

AN:

2054

South Asian (SAS)

AF:

0.00

AC:

AN:

2634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50662

Other (OTH)

AF:

0.00

AC:

AN:

1626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Benign

0.97

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.033

PhyloP100

1.8

Vest4

0.012

GERP RS

0.79

PromoterAI

0.0087

Neutral

(source)

Mutation Taster

=185/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.36

Position offset: -3

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