rs11033797

Positions:

• chr11-4769627-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001004752.2(OR51F1):​c.312T>C​(p.Tyr104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,604,308 control chromosomes in the GnomAD database, including 49,814 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 0.28 (6979 hom., cov: 32)
  • Exomes 𝑓: 0.23 (42835 hom.)
• Consequence: OR51F1 NM_001004752.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.599 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR51F1	NM_001004752.2	c.312T>C	p.Tyr104=	synonymous_variant	1/1	ENST00000624103.2	NP_001004752.2
MMP26	NM_021801.5	c.-145+2286A>G		intron_variant		ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-153+2286A>G		intron_variant			NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR51F1	ENST00000624103.2	c.312T>C	p.Tyr104=	synonymous_variant	1/1		NM_001004752.2	ENSP00000485387	P1
MMP26	ENST00000380390.6	c.-145+2286A>G		intron_variant		5	NM_021801.5	ENSP00000369753	P1
MMP26	ENST00000300762.2	c.-153+2286A>G		intron_variant		1		ENSP00000300762

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42532 AN: 151934 Hom.: 6967 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.301

GnomAD3 exomes AF: 0.207 AC: 51716 AN: 249918 Hom.: 6871 AF XY: 0.204 AC XY: 27543 AN XY: 135070

Gnomad AFR exome AF: 0.436

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0985

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.230 AC: 334160 AN: 1452256 Hom.: 42835 Cov.: 33 AF XY: 0.226 AC XY: 163704 AN XY: 722874

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.280 AC: 42592 AN: 152052 Hom.: 6979 Cov.: 32 AF XY: 0.269 AC XY: 20003 AN XY: 74338

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0990

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.299

Alfa AF: 0.275 Hom.: 6203

Bravo AF: 0.299

Asia WGS AF: 0.0780 AC: 272 AN: 3478

EpiCase AF: 0.270

EpiControl AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.77

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

LitVar

Other links and lift over

dbSNP: rs11033797; hg19: chr11-4790857; COSMIC: COSV58579948;