chr11-4954923-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001004748.1(OR51A2):c.791G>C(p.Arg264Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,176,860 control chromosomes in the GnomAD database, including 15 homozygotes. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R264L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00027 ( 6 hom., cov: 17)

Exomes 𝑓: 0.00019 ( 9 hom. )

Consequence

OR51A2
NM_001004748.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19

Publications

8 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]

OR51A2 links:

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]

MMP26 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51A2	NM_001004748.1 link	c.791G>C	p.Arg264Pro	missense_variant	Exon 1 of 1	ENST00000380371.1	NP_001004748.1	Q8NGJ7A0A126GWD5
MMP26	NM_021801.5 link	c.-144-33145C>G		intron_variant	Intron 2 of 7	ENST00000380390.6	NP_068573.2	Q9NRE1
MMP26	NM_001384608.1 link	c.-152-33347C>G		intron_variant	Intron 2 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR51A2	ENST00000380371.1 link	c.791G>C	p.Arg264Pro	missense_variant	Exon 1 of 1	6	NM_001004748.1	ENSP00000369729.1	Q8NGJ7
MMP26	ENST00000380390.6 link	c.-144-33145C>G		intron_variant	Intron 2 of 7	5	NM_021801.5	ENSP00000369753.1	Q9NRE1
MMP26	ENST00000300762.2 link	c.-152-33347C>G		intron_variant	Intron 2 of 7	1		ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

107282

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000299

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:

0.000609

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000107

AC:

AN:

196396

AF XY:

0.000113

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:

0.000235

Gnomad OTH exome

AF:

0.000209

GnomAD4 exome

AF:

0.000193

AC:

206

AN:

1069462

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

AN XY:

538310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29466

American (AMR)

AF:

0.00

AC:

AN:

33058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20560

East Asian (EAS)

AF:

0.00

AC:

AN:

33348

South Asian (SAS)

AF:

0.00

AC:

AN:

77092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4634

European-Non Finnish (NFE)

AF:

0.000247

AC:

193

AN:

781284

Other (OTH)

AF:

0.000280

AC:

AN:

46504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000270

AC:

AN:

107398

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

AN XY:

51906

show subpopulations

African (AFR)

AF:

0.0000298

AC:

AN:

33584

American (AMR)

AF:

0.00

AC:

AN:

9646

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2372

East Asian (EAS)

AF:

0.00

AC:

AN:

3736

South Asian (SAS)

AF:

0.00

AC:

AN:

3828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

196

European-Non Finnish (NFE)

AF:

0.000609

AC:

AN:

45948

Other (OTH)

AF:

0.00

AC:

AN:

1398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000467

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 04, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.791G>C (p.R264P) alteration is located in exon 1 (coding exon 1) of the OR51A2 gene. This alteration results from a G to C substitution at nucleotide position 791, causing the arginine (R) at amino acid position 264 to be replaced by a proline (P). 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

0.30

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0085

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.75

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.8

PhyloP100

2.2

PROVEAN

Pathogenic

-6.5

REVEL

Benign

0.20

Sift

Uncertain

0.016

Sift4G

Uncertain

0.011

Polyphen

0.15

Vest4

0.71

MVP

0.94

MPC

2.0

ClinPred

0.24

GERP RS

0.19

Varity_R

0.77

gMVP

0.49

Mutation Taster

=98/2

polymorphism

(source)

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

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chr11-4954923-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over