11-4769013-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001004752.2(OR51F1):c.926G>C(p.Arg309Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,518,772 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R309H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000095 ( 0 hom. )

Consequence

OR51F1
NM_001004752.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0780

Publications

3 publications found

Variant links:

Genes affected

OR51F1 (HGNC:15196): (olfactory receptor family 51 subfamily F member 1) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

OR51F1 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51F1	NM_001004752.2 link	c.926G>C	p.Arg309Pro	missense_variant	Exon 1 of 1	ENST00000624103.2	NP_001004752.2	A6NLW9
MMP26	NM_021801.5 link	c.-145+1672C>G		intron_variant	Intron 2 of 7	ENST00000380390.6	NP_068573.2	Q9NRE1
MMP26	NM_001384608.1 link	c.-153+1672C>G		intron_variant	Intron 2 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OR51F1	ENST00000624103.2 link	c.926G>C	p.Arg309Pro	missense_variant	Exon 1 of 1	6	NM_001004752.2	ENSP00000485387.2	A6NGY5A6NLW9
MMP26	ENST00000380390.6 link	c.-145+1672C>G		intron_variant	Intron 2 of 7	5	NM_021801.5	ENSP00000369753.1	Q9NRE1
MMP26	ENST00000300762.2 link	c.-153+1672C>G		intron_variant	Intron 2 of 7	1		ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000951

AC:

AN:

1366736

Hom.:

Cov.:

AF XY:

0.0000105

AC XY:

AN XY:

669306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30306

American (AMR)

AF:

0.00

AC:

AN:

30166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19912

East Asian (EAS)

AF:

0.00

AC:

AN:

38876

South Asian (SAS)

AF:

0.00

AC:

AN:

70188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5292

European-Non Finnish (NFE)

AF:

0.0000122

AC:

AN:

1065920

Other (OTH)

AF:

0.00

AC:

AN:

56242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152036

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41382

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.29

LIST_S2

Uncertain

0.86

D;T

M_CAP

Benign

0.0099

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-0.53

MutationAssessor

Pathogenic

4.4

.;H

PhyloP100

0.078

PrimateAI

Benign

0.18

PROVEAN

Pathogenic

-5.4

.;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

.;D

Polyphen

1.0

.;D

Vest4

0.58

MutPred

0.62

.;Loss of MoRF binding (P = 6e-04);

MVP

0.58

ClinPred

1.0

GERP RS

2.6

Varity_R

0.81

gMVP

0.84

Mutation Taster

=100/0

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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11-4769013-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over