chr9-135548765-A-G

Position:

chr9-135548765-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014582.3(OBP2A):c.446A>G(p.His149Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

OBP2A
NM_014582.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -6.49

Variant links:

Genes affected

OBP2A (HGNC:23380): (odorant binding protein 2A) This gene encodes a small extracellular protein belonging to the lipocalin superfamily. The protein is thought to transport small, hydrophobic, volatile molecules or odorants through the nasal mucus to olfactory receptors, and may also function as a scavenger of highly concentrated or toxic odors. The protein is expressed as a monomer in the nasal mucus, and can bind diverse types of odorants with a higher affinity for aldehydes and fatty acids. This gene and a highly similar family member are located in a cluster of lipocalin genes on chromosome 9. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

OBP2A links:

OBP2A (HGNC:):

OBP2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009886503).

BP6

Variant 9-135548765-A-G is Benign according to our data. Variant chr9-135548765-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2385929.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OBP2A	NM_014582.3 linkuse as main transcript	c.446A>G	p.His149Arg	missense_variant	5/7	ENST00000371776.6	NP_055397.1	Q9NY56-1
OBP2A	NM_001293189.2 linkuse as main transcript	c.511A>G	p.Thr171Ala	missense_variant	5/7		NP_001280118.1	Q9NY56Q5T8A5B7ZLH4
OBP2A	NM_001293193.2 linkuse as main transcript	c.377A>G	p.His126Arg	missense_variant	4/6		NP_001280122.1	Q9NY56Q5T8A4
OBP2A	NR_120603.2 linkuse as main transcript	n.550A>G		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OBP2A	ENST00000371776.6 linkuse as main transcript	c.446A>G	p.His149Arg	missense_variant	5/7	1	NM_014582.3	ENSP00000360841.1		Q9NY56-1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000994

AC:

AN:

251444

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461752

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0010

DANN

Benign

0.15

DEOGEN2

Benign

0.0011

.;T;T

Eigen

Benign

-2.7

Eigen_PC

Benign

-2.7

FATHMM_MKL

Benign

0.00072

LIST_S2

Benign

0.16

T;.;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.0099

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.55

.;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.30

N;N;N

REVEL

Benign

0.0060

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.98

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.029

MVP

0.11

MPC

0.30

ClinPred

0.020

GERP RS

-5.0

Varity_R

0.067

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over