rs755621211

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001005328.2(OR2A7):c.257A>T(p.His86Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 19)

Exomes 𝑓: 0.00070 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR2A7
NM_001005328.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.27

Publications

1 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=0.03725314).

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.257A>T	p.His86Leu	missense	Exon 2 of 2	NP_001005328.1	Q96R45
ARHGEF34P	NR_033942.1		n.3828A>T		non_coding_transcript_exon	Exon 13 of 13
ARHGEF35-AS1	NR_126022.1		n.494-21100T>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR2A7	ENST00000641841.1	MANE Select	c.257A>T	p.His86Leu	missense	Exon 2 of 2	ENSP00000493320.1	Q96R45
OR2A7	ENST00000493325.1	TSL:6	c.257A>T	p.His86Leu	missense	Exon 1 of 1	ENSP00000420502.1	Q96R45
ARHGEF35-AS1	ENST00000460955.5	TSL:4	n.494-21100T>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

196

AN:

125984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00505

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00163

Gnomad EAS

AF:

0.000207

Gnomad SAS

AF:

0.000805

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00373

Gnomad NFE

AF:

0.000411

Gnomad OTH

AF:

0.00123

GnomAD2 exomes

AF:

0.000489

AC:

AN:

169704

AF XY:

0.000425

show subpopulations

Gnomad AFR exome

AF:

0.00713

Gnomad AMR exome

AF:

0.000465

Gnomad ASJ exome

AF:

0.000276

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000544

Gnomad OTH exome

AF:

0.000881

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000703

AC:

731

AN:

1040194

Hom.:

Cov.:

AF XY:

0.000677

AC XY:

357

AN XY:

527372

show subpopulations

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

African (AFR)

AF:

0.0101

AC:

204

AN:

20202

American (AMR)

AF:

0.000780

AC:

AN:

37156

Ashkenazi Jewish (ASJ)

AF:

0.00285

AC:

AN:

21720

East Asian (EAS)

AF:

0.00

AC:

AN:

37238

South Asian (SAS)

AF:

0.000248

AC:

AN:

72522

European-Finnish (FIN)

AF:

0.0000216

AC:

AN:

46206

Middle Eastern (MID)

AF:

0.00268

AC:

AN:

3726

European-Non Finnish (NFE)

AF:

0.000454

AC:

343

AN:

755902

Other (OTH)

AF:

0.00141

AC:

AN:

45522

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.188

Heterozygous variant carriers

125

187

250

312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00155

AC:

196

AN:

126084

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

AN XY:

60642

show subpopulations

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

African (AFR)

AF:

0.00503

AC:

150

AN:

29808

American (AMR)

AF:

0.000720

AC:

AN:

12500

Ashkenazi Jewish (ASJ)

AF:

0.00163

AC:

AN:

3068

East Asian (EAS)

AF:

0.000208

AC:

AN:

4808

South Asian (SAS)

AF:

0.000806

AC:

AN:

3720

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8568

Middle Eastern (MID)

AF:

0.00403

AC:

AN:

248

European-Non Finnish (NFE)

AF:

0.000411

AC:

AN:

60884

Other (OTH)

AF:

0.00121

AC:

AN:

1648

⚠️ 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: 0.258

Heterozygous variant carriers

104

130

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:

0.00294

Hom.:

ExAC

AF:

0.0000176

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.1

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0056

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.010

M_CAP

Benign

0.0013

MetaRNN

Benign

0.037

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.47

PhyloP100

-3.3

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.7

REVEL

Benign

0.029

Sift

Benign

0.23

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.12

MutPred

0.28

Loss of methylation at K89 (P = 0.0617)

MVP

0.16

ClinPred

0.0011

GERP RS

-2.4

PromoterAI

0.019

Neutral

(source)

Varity_R

0.085

gMVP

0.15

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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