rs12788102

Variant names:

• chr11-4769345-A-G
• rs12788102
• NM_001004752.2:c.594T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001004752.2(OR51F1):​c.594T>C​(p.Cys198Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,612,344 control chromosomes in the GnomAD database, including 11,677 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.094 (846 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10831 hom.)
• Consequence: OR51F1 NM_001004752.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186
• Publications: 24 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.186 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR51F1	NM_001004752.2	c.594T>C	p.Cys198Cys	synonymous_variant	Exon 1 of 1	ENST00000624103.2	NP_001004752.2
MMP26	NM_021801.5	c.-145+2004A>G		intron_variant	Intron 2 of 7	ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-153+2004A>G		intron_variant	Intron 2 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR51F1	ENST00000624103.2	c.594T>C	p.Cys198Cys	synonymous_variant	Exon 1 of 1	6	NM_001004752.2	ENSP00000485387.2
MMP26	ENST00000380390.6	c.-145+2004A>G		intron_variant	Intron 2 of 7	5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-153+2004A>G		intron_variant	Intron 2 of 7	1		ENSP00000300762.2

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14382 AN: 152166 Hom.: 847 Cov.: 32

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.116

GnomAD2 exomes AF: 0.0952 AC: 23943 AN: 251466 AF XY: 0.0958

Gnomad AFR exome AF: 0.0379

Gnomad AMR exome AF: 0.0731

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.115 AC: 168360 AN: 1460060 Hom.: 10831 Cov.: 33 AF XY: 0.113 AC XY: 82090 AN XY: 726408

African (AFR) AF: 0.0395 AC: 1323 AN: 33468

American (AMR) AF: 0.0777 AC: 3474 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 4299 AN: 26110

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.0265 AC: 2288 AN: 86244

European-Finnish (FIN) AF: 0.123 AC: 6591 AN: 53420

Middle Eastern (MID) AF: 0.133 AC: 765 AN: 5768

European-Non Finnish (NFE) AF: 0.128 AC: 142614 AN: 1110300

Other (OTH) AF: 0.116 AC: 6996 AN: 60328

GnomAD4 genome AF: 0.0945 AC: 14387 AN: 152284 Hom.: 846 Cov.: 32 AF XY: 0.0915 AC XY: 6818 AN XY: 74474

African (AFR) AF: 0.0411 AC: 1708 AN: 41572

American (AMR) AF: 0.109 AC: 1670 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3468

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0265 AC: 128 AN: 4830

European-Finnish (FIN) AF: 0.123 AC: 1301 AN: 10610

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8633 AN: 67998

Other (OTH) AF: 0.116 AC: 245 AN: 2114

Alfa AF: 0.116 Hom.: 3621

Bravo AF: 0.0954

Asia WGS AF: 0.0220 AC: 77 AN: 3478

EpiCase AF: 0.136

EpiControl AF: 0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.2
DANN	Benign	0.66
PhyloP100		0.19
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12788102; hg19: chr11-4790575; COSMIC: COSV58579771;