Genetic Variant OR5AN1:p.Ala275Glu (chr11-59365282-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004729.2(OR5AN1):c.824C>A(p.Ala275Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A275V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OR5AN1
NM_001004729.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.398

Publications

1 publications found

Variant links:

Genes affected

OR5AN1 (HGNC:15255): (olfactory receptor family 5 subfamily AN 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]

OR5AN1 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26052815).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004729.2. 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
	OR5AN1	NM_001004729.2	MANE Select	c.824C>A	p.Ala275Glu	missense	Exon 2 of 2	NP_001004729.1	A0A126GVP9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR5AN1	ENST00000641998.1	MANE Select	c.824C>A	p.Ala275Glu	missense	Exon 2 of 2	ENSP00000493250.1	Q8NGI8
OR5AN1	ENST00000313940.2	TSL:6	c.824C>A	p.Ala275Glu	missense	Exon 1 of 1	ENSP00000320302.2	Q8NGI8
OR5AN1	ENST00000641850.1		c.824C>A	p.Ala275Glu	missense	Exon 2 of 2	ENSP00000492957.1	Q8NGI8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459014

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726036

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33438

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39660

South Asian (SAS)

AF:

0.00

AC:

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1109546

Other (OTH)

AF:

0.00

AC:

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

Eigen

Benign

-0.022

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.84

M_CAP

Benign

0.0092

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.8

PhyloP100

-0.40

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.20

Sift

Uncertain

0.025

Sift4G

Uncertain

0.0080

Polyphen

0.98

Vest4

0.44

MVP

0.46

MPC

0.012

ClinPred

0.95

GERP RS

1.6

Varity_R

0.67

gMVP

0.17

Mutation Taster

=98/2

polymorphism

(source)

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

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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