Variant 11-58507798-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005218.3(OR5B21):c.308T>G(p.Val103Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,613,996 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 0.00027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

OR5B21
NM_001005218.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.470

Variant links:

Genes affected

OR5B21 (HGNC:19616): (olfactory receptor family 5 subfamily B member 21) 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]

OR5B21 links:

LOC105369313 (HGNC:):

LOC105369313 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02973935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5B21	NM_001005218.3 linkuse as main transcript	c.308T>G	p.Val103Gly	missense_variant	1/1	ENST00000360374.3	NP_001005218.1	A6NL26
LOC105369313	XR_007062673.1 linkuse as main transcript	n.239-2256T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5B21	ENST00000360374.3 linkuse as main transcript	c.308T>G	p.Val103Gly	missense_variant	1/1	6	NM_001005218.3	ENSP00000353537.2		A6NL26

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.000544

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000128

AC:

AN:

250426

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135298

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000257

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000224

AC:

328

AN:

1461758

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

156

AN XY:

727154

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:

0.00

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000278

Gnomad4 OTH exome

AF:

0.000182

GnomAD4 genome

AF:

0.000269

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.000544

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000275

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

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

Feb 07, 2023

The c.308T>G (p.V103G) alteration is located in exon 1 (coding exon 1) of the OR5B21 gene. This alteration results from a T to G substitution at nucleotide position 308, causing the valine (V) at amino acid position 103 to be replaced by a glycine (G). 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

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.5

DANN

Benign

0.91

DEOGEN2

Benign

0.020

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.23

M_CAP

Benign

0.0038

MetaRNN

Benign

0.030

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.75

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.092

Sift

Benign

0.39

Sift4G

Benign

0.49

Polyphen

0.0030

Vest4

0.37

MVP

0.10

MPC

0.028

ClinPred

0.017

GERP RS

-1.5

Varity_R

0.20

gMVP

0.26

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