11-6785440-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001004489.3(OR2AG1):c.403C>G(p.Leu135Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,614,138 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 40 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 37 hom. )

Consequence

OR2AG1
NM_001004489.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.647

Publications

3 publications found

Variant links:

Genes affected

OR2AG1 (HGNC:15142): (olfactory receptor family 2 subfamily AG 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

OR2AG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035690963).

BP6

Variant 11-6785440-C-G is Benign according to our data. Variant chr11-6785440-C-G is described in ClinVar as Benign. ClinVar VariationId is 776576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0112 (1705/152274) while in subpopulation AFR AF = 0.0386 (1605/41544). AF 95% confidence interval is 0.0371. There are 40 homozygotes in GnomAd4. There are 790 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 40 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004489.3. 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
	OR2AG1	NM_001004489.3	MANE Select	c.403C>G	p.Leu135Val	missense	Exon 2 of 2	NP_001004489.1	A0A126GVD0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2AG1	ENST00000641258.1	MANE Select	c.403C>G	p.Leu135Val	missense	Exon 2 of 2	ENSP00000493074.1	Q9H205
	OR2AG1	ENST00000641344.1		n.837+38C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1696

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0385

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00957

GnomAD2 exomes

AF:

0.00299

AC:

750

AN:

250970

AF XY:

0.00210

show subpopulations

Gnomad AFR exome

AF:

0.0404

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.00122

AC:

1778

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

785

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0402

AC:

1347

AN:

33478

American (AMR)

AF:

0.00188

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000139

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00537

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000119

AC:

132

AN:

1111992

Other (OTH)

AF:

0.00280

AC:

169

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

111

222

333

444

555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.0112

AC:

1705

AN:

152274

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

790

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0386

AC:

1605

AN:

41544

American (AMR)

AF:

0.00405

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68028

Other (OTH)

AF:

0.00947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

166

248

331

414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00359

Hom.:

Bravo

AF:

0.0129

ESP6500AA

AF:

0.0384

AC:

169

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.00387

AC:

470

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.1

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.037

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0036

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

PhyloP100

-0.65

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.042

Sift

Benign

0.048

Polyphen

0.25

Vest4

0.016

MVP

0.16

MPC

0.040

ClinPred

0.0052

GERP RS

0.19

Varity_R

0.048

gMVP

0.056

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over