Variant 9-133208549-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014581.4(OBP2B):c.126G>T(p.Glu42Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,230 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

OBP2B
NM_014581.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.242

Variant links:

Genes affected

OBP2B (HGNC:23381): (odorant binding protein 2B) Predicted to enable small molecule binding activity. Predicted to be involved in chemosensory behavior. Predicted to be located in extracellular region. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

OBP2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0861257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OBP2B	NM_014581.4 link	c.126G>T	p.Glu42Asp	missense_variant	2/7	ENST00000372034.8	NP_055396.1	Q9NPH6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OBP2B	ENST00000372034.8 link	c.126G>T	p.Glu42Asp	missense_variant	2/7	1	NM_014581.4	ENSP00000361104.3	Q9NPH6-1
OBP2B	ENST00000618116.4 link	c.126G>T	p.Glu42Asp	missense_variant	2/7	1		ENSP00000484615.1	Q9NPH6-1
OBP2B	ENST00000473737.5 link	n.126G>T		non_coding_transcript_exon_variant	2/8	1		ENSP00000434927.1	Q9NPH6-2
OBP2B	ENST00000461961.2 link	n.115-346G>T		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000363

AC:

AN:

247740

Hom.:

AF XY:

0.0000523

AC XY:

AN XY:

133920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000716

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461104

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.126G>T (p.E42D) alteration is located in exon 2 (coding exon 2) of the OBP2B gene. This alteration results from a G to T substitution at nucleotide position 126, causing the glutamic acid (E) at amino acid position 42 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.3

DANN

Uncertain

0.98

DEOGEN2

Benign

0.067

T;T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.47

.;T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.086

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.5

L;L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

N;.;.

REVEL

Benign

0.0090

Sift

Benign

0.28

T;.;.

Sift4G

Benign

0.60

T;T;T

Polyphen

0.33

B;B;.

Vest4

0.090

MutPred

0.46

Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);

MVP

0.29

MPC

2.2

ClinPred

0.085

GERP RS

1.3

Varity_R

0.056

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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