rs752232056

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001004748.1(OR51A2):​c.740G>T​(p.Cys247Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts 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. C247Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 18)
Exomes 𝑓: 0.0000016 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

OR51A2
NM_001004748.1 missense

Scores

1
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0960

Publications

4 publications found
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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.36590686).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OR51A2NM_001004748.1 linkc.740G>T p.Cys247Phe missense_variant Exon 1 of 1 ENST00000380371.1 NP_001004748.1 Q8NGJ7A0A126GWD5
MMP26NM_021801.5 linkc.-144-33094C>A intron_variant Intron 2 of 7 ENST00000380390.6 NP_068573.2 Q9NRE1
MMP26NM_001384608.1 linkc.-152-33296C>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.740G>T p.Cys247Phe missense_variant Exon 1 of 1 6 NM_001004748.1 ENSP00000369729.1 Q8NGJ7
MMP26ENST00000380390.6 linkc.-144-33094C>A intron_variant Intron 2 of 7 5 NM_021801.5 ENSP00000369753.1 Q9NRE1
MMP26ENST00000300762.2 linkc.-152-33296C>A intron_variant Intron 2 of 7 1 ENSP00000300762.2 A0A8J8YUH5

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
116792
Hom.:
0
Cov.:
18
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000467
AC:
1
AN:
214300
AF XY:
0.00000862
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000161
AC:
2
AN:
1242398
Hom.:
0
Cov.:
32
AF XY:
0.00000322
AC XY:
2
AN XY:
621538
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31348
American (AMR)
AF:
0.00
AC:
0
AN:
35422
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23260
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34396
South Asian (SAS)
AF:
0.0000248
AC:
2
AN:
80716
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
46960
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5168
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
932398
Other (OTH)
AF:
0.00
AC:
0
AN:
52730
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
116906
Hom.:
0
Cov.:
18
AF XY:
0.00
AC XY:
0
AN XY:
56430
African (AFR)
AF:
0.00
AC:
0
AN:
35412
American (AMR)
AF:
0.00
AC:
0
AN:
10396
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2692
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4002
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4018
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
7018
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
244
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
51158
Other (OTH)
AF:
0.00
AC:
0
AN:
1540
Alfa
AF:
0.00
Hom.:
0
ExAC
AF:
0.00000916
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.012
T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.37
T
MetaSVM
Benign
-0.79
T
MutationAssessor
Uncertain
2.2
M
PhyloP100
0.096
PROVEAN
Pathogenic
-8.0
D
REVEL
Benign
0.17
Sift
Benign
0.068
T
Sift4G
Uncertain
0.036
D
Polyphen
0.73
P
Vest4
0.42
MutPred
0.46
Gain of catalytic residue at C242 (P = 0.1303);
MVP
0.70
MPC
2.1
ClinPred
0.54
D
GERP RS
3.3
Varity_R
0.46
gMVP
0.095
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.20
Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs752232056; hg19: chr11-4976204; COSMIC: COSV100985030; API