chr7-99876804-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001005276.1(OR2AE1):c.230T>C(p.Ile77Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,613,364 control chromosomes in the GnomAD database, including 229,798 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. I77V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.60 ( 29150 hom., cov: 30)

Exomes 𝑓: 0.52 ( 200648 hom. )

Consequence

OR2AE1
NM_001005276.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0900

Publications

48 publications found

Variant links:

Genes affected

OR2AE1 (HGNC:15087): (olfactory receptor family 2 subfamily AE 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]

OR2AE1 links:

TRIM4 (HGNC:16275): (tripartite motif containing 4) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. Its function has not been identified. Alternatively spliced transcript variants that encode different isoforms have been described.[provided by RefSeq, Jul 2010]

TRIM4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.4334534E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005276.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2AE1	NM_001005276.1	MANE Select	c.230T>C	p.Ile77Thr	missense	Exon 1 of 1	NP_001005276.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2AE1	ENST00000316368.3	TSL:6 MANE Select	c.230T>C	p.Ile77Thr	missense	Exon 1 of 1	ENSP00000313936.2
	TRIM4	ENST00000447480.5	TSL:3	c.*186T>C		downstream_gene	N/A	ENSP00000396229.1

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90607

AN:

151764

Hom.:

29098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.846

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.476

Gnomad FIN

AF:

0.547

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.528

Gnomad OTH

AF:

0.545

GnomAD2 exomes

AF:

0.509

AC:

127943

AN:

251396

AF XY:

0.503

show subpopulations

Gnomad AFR exome

AF:

0.858

Gnomad AMR exome

AF:

0.456

Gnomad ASJ exome

AF:

0.442

Gnomad EAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.541

Gnomad NFE exome

AF:

0.525

Gnomad OTH exome

AF:

0.484

GnomAD4 exome

AF:

0.519

AC:

758023

AN:

1461482

Hom.:

200648

Cov.:

AF XY:

0.515

AC XY:

374506

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.856

AC:

28654

AN:

33478

American (AMR)

AF:

0.455

AC:

20359

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

11589

AN:

26130

East Asian (EAS)

AF:

0.290

AC:

11525

AN:

39698

South Asian (SAS)

AF:

0.463

AC:

39905

AN:

86244

European-Finnish (FIN)

AF:

0.543

AC:

28977

AN:

53408

Middle Eastern (MID)

AF:

0.374

AC:

2156

AN:

5768

European-Non Finnish (NFE)

AF:

0.525

AC:

584069

AN:

1111638

Other (OTH)

AF:

0.510

AC:

30789

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

20846

41692

62539

83385

104231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16688

33376

50064

66752

83440

<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:

0.597

AC:

90714

AN:

151882

Hom.:

29150

Cov.:

AF XY:

0.590

AC XY:

43799

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.846

AC:

35065

AN:

41440

American (AMR)

AF:

0.465

AC:

7102

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

1545

AN:

3466

East Asian (EAS)

AF:

0.288

AC:

1478

AN:

5138

South Asian (SAS)

AF:

0.475

AC:

2277

AN:

4796

European-Finnish (FIN)

AF:

0.547

AC:

5756

AN:

10520

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.528

AC:

35884

AN:

67942

Other (OTH)

AF:

0.542

AC:

1143

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1649

3299

4948

6598

8247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

736

1472

2208

2944

3680

<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:

0.540

Hom.:

89703

Bravo

AF:

0.600

TwinsUK

AF:

0.525

AC:

1946

ALSPAC

AF:

0.527

AC:

2030

ESP6500AA

AF:

0.837

AC:

3687

ESP6500EA

AF:

0.522

AC:

4489

ExAC

AF:

0.520

AC:

63178

Asia WGS

AF:

0.455

AC:

1583

AN:

3478

EpiCase

AF:

0.509

EpiControl

AF:

0.508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

6.8

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.00024

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.43

MetaRNN

Benign

6.4e-7

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.48

PhyloP100

-0.090

PrimateAI

Benign

0.34

PROVEAN

Benign

0.61

REVEL

Benign

0.020

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.0060

MPC

0.043

ClinPred

0.0032

GERP RS

0.81

PromoterAI

-0.0013

Neutral

(source)

Varity_R

0.048

gMVP

0.056

Mutation Taster

=100/0

polymorphism (auto)

(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