11-4954923-C-A

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>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. 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. 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

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 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004748.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR51A2	NM_001004748.1	MANE Select	c.791G>T	p.Arg264Leu	missense	Exon 1 of 1	NP_001004748.1	Q8NGJ7
MMP26	NM_021801.5	MANE Select	c.-144-33145C>A		intron	N/A	NP_068573.2	Q9NRE1
MMP26	NM_001384608.1		c.-152-33347C>A		intron	N/A	NP_001371537.1	A0A8J8YUH5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OR51A2	ENST00000380371.1	TSL:6 MANE Select	c.791G>T	p.Arg264Leu	missense	Exon 1 of 1	ENSP00000369729.1	Q8NGJ7
MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-144-33145C>A		intron	N/A	ENSP00000369753.1	Q9NRE1
MMP26	ENST00000300762.2	TSL:1	c.-152-33347C>A		intron	N/A	ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes

AF:

0.000168

AC:

AN:

107280

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000662

AC:

AN:

196396

AF XY:

0.0000848

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:

0.000153

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000163

AC:

174

AN:

1069466

Hom.:

Cov.:

AF XY:

0.000165

AC XY:

AN XY:

538314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29466

American (AMR)

AF:

0.0000302

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:

0.000218

AC:

170

AN:

781288

Other (OTH)

AF:

0.0000645

AC:

AN:

46504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000168

AC:

AN:

107280

Hom.:

Cov.:

AF XY:

0.0000772

AC XY:

AN XY:

51790

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.000208

AC:

AN:

9628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2372

East Asian (EAS)

AF:

0.00

AC:

AN:

3740

South Asian (SAS)

AF:

0.00

AC:

AN:

3836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

208

European-Non Finnish (NFE)

AF:

0.000348

AC:

AN:

45948

Other (OTH)

AF:

0.00

AC:

AN:

1386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.594

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00297

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000259

AC:

ExAC

AF:

0.0000467

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0089

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.79

M_CAP

Benign

0.029

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.8

PhyloP100

2.2

PROVEAN

Pathogenic

-6.6

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.97

Vest4

0.63

MVP

0.78

MPC

2.5

ClinPred

0.65

GERP RS

0.19

Varity_R

0.41

gMVP

0.15

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over