rs61744535

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001004748.1(OR51A2):​c.791G>T​(p.Arg264Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,176,746 control chromosomes in the GnomAD database, including 52 homozygotes. 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. R264P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00017 ( 5 hom., cov: 17)
Exomes 𝑓: 0.00016 ( 47 hom. )

Consequence

OR51A2
NM_001004748.1 missense

Scores

3
3
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.19
Variant links:
Genes affected
OR51A2 (HGNC:14764): (olfactory receptor family 51 subfamily A member 2) 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]
MMP26 (HGNC:14249): (matrix metallopeptidase 26) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR51A2NM_001004748.1 linkc.791G>T p.Arg264Leu missense_variant Exon 1 of 1 ENST00000380371.1 NP_001004748.1 Q8NGJ7A0A126GWD5
MMP26NM_021801.5 linkc.-144-33145C>A intron_variant Intron 2 of 7 ENST00000380390.6 NP_068573.2 Q9NRE1
MMP26NM_001384608.1 linkc.-152-33347C>A intron_variant Intron 2 of 7 NP_001371537.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OR51A2ENST00000380371.1 linkc.791G>T p.Arg264Leu missense_variant Exon 1 of 1 6 NM_001004748.1 ENSP00000369729.1 Q8NGJ7
MMP26ENST00000380390.6 linkc.-144-33145C>A intron_variant Intron 2 of 7 5 NM_021801.5 ENSP00000369753.1 Q9NRE1
MMP26ENST00000300762.2 linkc.-152-33347C>A intron_variant Intron 2 of 7 1 ENSP00000300762.2 A0A8J8YUH5

Frequencies

GnomAD3 genomes
AF:
0.000168
AC:
18
AN:
107280
Hom.:
5
Cov.:
17
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000208
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:
0.000348
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000662
AC:
13
AN:
196396
Hom.:
4
AF XY:
0.0000848
AC XY:
9
AN XY:
106082
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000153
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000163
AC:
174
AN:
1069466
Hom.:
47
Cov.:
32
AF XY:
0.000165
AC XY:
89
AN XY:
538314
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000302
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000218
Gnomad4 OTH exome
AF:
0.0000645
GnomAD4 genome
AF:
0.000168
AC:
18
AN:
107280
Hom.:
5
Cov.:
17
AF XY:
0.0000772
AC XY:
4
AN XY:
51790
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000208
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000348
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00242
Hom.:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000259
AC:
2
ExAC
AF:
0.0000467
AC:
5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0089
T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.029
D
MetaRNN
Uncertain
0.72
D
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.8
M
PROVEAN
Pathogenic
-6.6
D
REVEL
Benign
0.17
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.97
D
Vest4
0.63
MVP
0.78
MPC
2.5
ClinPred
0.65
D
GERP RS
0.19
Varity_R
0.41
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs61744535; hg19: chr11-4976153; API