Genetic Variant OR2A7:p.Val152Leu (chr7-144259175-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005328.2(OR2A7):c.454G>C(p.Val152Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. V152I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000091 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0000084 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR2A7
NM_001005328.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.51

Publications

0 publications found

Variant links:

Genes affected

OR2A7 (HGNC:8234): (olfactory receptor family 2 subfamily A member 7) 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]

OR2A7 links:

ARHGEF34P (HGNC:38086): (Rho guanine nucleotide exchange factor 34, pseudogene)

ARHGEF34P links:

ARHGEF35-AS1 (HGNC:41292): (ARHGEF35 antisense RNA 1)

ARHGEF35-AS1 links:

OR2A1-AS1 (HGNC:49168): (OR2A1 antisense RNA 1)

OR2A1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0585607).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005328.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR2A7	NM_001005328.2	MANE Select	c.454G>C	p.Val152Leu	missense	Exon 2 of 2	NP_001005328.1	Q96R45
ARHGEF34P	NR_033942.1		n.4025G>C		non_coding_transcript_exon	Exon 13 of 13
ARHGEF35-AS1	NR_126022.1		n.494-21297C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR2A7	ENST00000641841.1	MANE Select	c.454G>C	p.Val152Leu	missense	Exon 2 of 2	ENSP00000493320.1	Q96R45
OR2A7	ENST00000493325.1	TSL:6	c.454G>C	p.Val152Leu	missense	Exon 1 of 1	ENSP00000420502.1	Q96R45
ARHGEF35-AS1	ENST00000460955.5	TSL:4	n.494-21297C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000913

AC:

AN:

131408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000342

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:

0.00000761

AC:

AN:

131486

AF XY:

0.0000142

show subpopulations

Gnomad AFR exome

AF:

0.000132

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000843

AC:

AN:

1068026

Hom.:

Cov.:

AF XY:

0.00000742

AC XY:

AN XY:

538822

show subpopulations

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

African (AFR)

AF:

0.000356

AC:

AN:

25302

American (AMR)

AF:

0.00

AC:

AN:

34824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22148

East Asian (EAS)

AF:

0.00

AC:

AN:

36842

South Asian (SAS)

AF:

0.00

AC:

AN:

72124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46086

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4178

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

779640

Other (OTH)

AF:

0.00

AC:

AN:

46882

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000509044), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.308

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000913

AC:

AN:

131408

Hom.:

Cov.:

AF XY:

0.0000479

AC XY:

AN XY:

62672

show subpopulations

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

African (AFR)

AF:

0.000342

AC:

AN:

35116

American (AMR)

AF:

0.00

AC:

AN:

12706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3164

East Asian (EAS)

AF:

0.00

AC:

AN:

5010

South Asian (SAS)

AF:

0.00

AC:

AN:

3758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

60892

Other (OTH)

AF:

0.00

AC:

AN:

1706

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.292

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000295

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.26

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.0017

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.042

M_CAP

Benign

0.0070

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.2

MutationAssessor

Benign

-0.81

PhyloP100

-1.5

PrimateAI

Benign

0.26

PROVEAN

Benign

0.40

REVEL

Benign

0.015

Sift

Benign

0.32

Sift4G

Benign

0.33

Polyphen

0.0060

Vest4

0.090

MVP

0.076

ClinPred

0.028

GERP RS

0.93

Varity_R

0.035

gMVP

0.082

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over