11-4769116-G-A

Position:

chr11-4769116-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001004752.2(OR51F1):c.823C>T(p.Arg275Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,605,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

OR51F1
NM_001004752.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0340

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051761627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OR51F1	NM_001004752.2 linkuse as main transcript	c.823C>T	p.Arg275Trp	missense_variant	1/1	ENST00000624103.2	NP_001004752.2
MMP26	NM_021801.5 linkuse as main transcript	c.-145+1775G>A		intron_variant		ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1 linkuse as main transcript	c.-153+1775G>A		intron_variant			NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
OR51F1	ENST00000624103.2 linkuse as main transcript	c.823C>T	p.Arg275Trp	missense_variant	1/1		NM_001004752.2	ENSP00000485387	P1
MMP26	ENST00000380390.6 linkuse as main transcript	c.-145+1775G>A		intron_variant		5	NM_021801.5	ENSP00000369753	P1
MMP26	ENST00000300762.2 linkuse as main transcript	c.-153+1775G>A		intron_variant		1		ENSP00000300762

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000251

AC:

AN:

243246

Hom.:

AF XY:

0.000267

AC XY:

AN XY:

131024

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.000380

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000349

Gnomad FIN exome

AF:

0.000144

Gnomad NFE exome

AF:

0.000318

Gnomad OTH exome

AF:

0.000337

GnomAD4 exome

AF:

0.000187

AC:

272

AN:

1452728

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

122

AN XY:

721896

show subpopulations

Gnomad4 AFR exome

AF:

0.000450

Gnomad4 AMR exome

AF:

0.000338

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.000170

Gnomad4 NFE exome

AF:

0.000182

Gnomad4 OTH exome

AF:

0.000317

GnomAD4 genome

AF:

0.000177

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.000249

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000222

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.802C>T (p.R268W) alteration is located in exon 1 (coding exon 1) of the OR51F1 gene. This alteration results from a C to T substitution at nucleotide position 802, causing the arginine (R) at amino acid position 268 to be replaced by a tryptophan (W). 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

0.098

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.011

.;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.048

T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.5

.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.17

PROVEAN

Uncertain

-4.3

.;D

REVEL

Benign

0.026

Sift

Uncertain

0.017

.;D

Polyphen

0.99

.;D

Vest4

0.14

MVP

0.33

ClinPred

0.14

GERP RS

0.073

Varity_R

0.18

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over