rs145204134

Variant names:

• chr11-4769116-G-A
• rs145204134
• NM_001004752.2:c.823C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-4769116-G-A
• chr11-4769116-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 14/22 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. R275Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: OR51F1 NM_001004752.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0340
• Publications: 5 publications found

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.051761627).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004752.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR51F1	NM_001004752.2	MANE Select	c.823C>T	p.Arg275Trp	missense	Exon 1 of 1	NP_001004752.2	A6NGY5
	MMP26	NM_021801.5	MANE Select	c.-145+1775G>A		intron	N/A	NP_068573.2	Q9NRE1
	MMP26	NM_001384608.1		c.-153+1775G>A		intron	N/A	NP_001371537.1	A0A8J8YUH5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR51F1	ENST00000624103.2	TSL:6 MANE Select	c.823C>T	p.Arg275Trp	missense	Exon 1 of 1	ENSP00000485387.2	A6NGY5
	MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-145+1775G>A		intron	N/A	ENSP00000369753.1	Q9NRE1
	MMP26	ENST00000300762.2	TSL:1	c.-153+1775G>A		intron	N/A	ENSP00000300762.2	A0A8J8YUH5

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152156 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000251 AC: 61 AN: 243246 AF XY: 0.000267

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 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.: 0 Cov.: 33 AF XY: 0.000169 AC XY: 122 AN XY: 721896

African (AFR) AF: 0.000450 AC: 15 AN: 33338

American (AMR) AF: 0.000338 AC: 15 AN: 44322

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25080

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39664

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84448

European-Finnish (FIN) AF: 0.000170 AC: 9 AN: 52926

Middle Eastern (MID) AF: 0.00105 AC: 6 AN: 5722

European-Non Finnish (NFE) AF: 0.000182 AC: 202 AN: 1107214

Other (OTH) AF: 0.000317 AC: 19 AN: 60014

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15 AN XY: 74454

African (AFR) AF: 0.000193 AC: 8 AN: 41546

American (AMR) AF: 0.000196 AC: 3 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000270 Hom.: 0

Bravo AF: 0.000249

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000222 AC: 27

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.048	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.034
PrimateAI	Benign	0.17	T
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	T
GERP RS		0.073
Varity_R		0.18
gMVP		0.12
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs145204134; hg19: chr11-4790346; COSMIC: COSV104661718;