rs7941731

Positions:

• chr11-4803995-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005177.3(OR52R1):​c.386T>C​(p.Ile129Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,613,204 control chromosomes in the GnomAD database, including 92,350 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (11265 hom., cov: 29)
  • Exomes 𝑓: 0.32 (81085 hom.)
• Consequence: OR52R1 NM_001005177.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.18

Genes affected

OR52R1 (HGNC:15235): (olfactory receptor family 52 subfamily R 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017163455).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52R1	NM_001005177.3	c.386T>C	p.Ile129Thr	missense_variant	1/1	ENST00000624978.1	NP_001005177.3
MMP26	NM_021801.5	c.-145+36654A>G		intron_variant		ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-153+36654A>G		intron_variant			NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52R1	ENST00000624978.1	c.386T>C	p.Ile129Thr	missense_variant	1/1		NM_001005177.3	ENSP00000485292	P1
MMP26	ENST00000380390.6	c.-145+36654A>G		intron_variant		5	NM_021801.5	ENSP00000369753	P1
MMP26	ENST00000300762.2	c.-153+36654A>G		intron_variant		1		ENSP00000300762

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55490 AN: 151304 Hom.: 11239 Cov.: 29

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.412

GnomAD3 exomes AF: 0.298 AC: 74801 AN: 250864 Hom.: 13297 AF XY: 0.301 AC XY: 40825 AN XY: 135544

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.532

Gnomad EAS exome AF: 0.0183

Gnomad SAS exome AF: 0.252

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.340

Gnomad OTH exome AF: 0.342

GnomAD4 exome AF: 0.323 AC: 471504 AN: 1461784 Hom.: 81085 Cov.: 46 AF XY: 0.322 AC XY: 234116 AN XY: 727188

Gnomad4 AFR exome AF: 0.527

Gnomad4 AMR exome AF: 0.211

Gnomad4 ASJ exome AF: 0.529

Gnomad4 EAS exome AF: 0.0217

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.346

GnomAD4 genome AF: 0.367 AC: 55570 AN: 151420 Hom.: 11265 Cov.: 29 AF XY: 0.358 AC XY: 26489 AN XY: 73974

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.0196

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.410

Alfa AF: 0.356 Hom.: 17402

Bravo AF: 0.381

TwinsUK AF: 0.335 AC: 1244

ALSPAC AF: 0.326 AC: 1258

ESP6500AA AF: 0.515 AC: 2266

ESP6500EA AF: 0.350 AC: 3011

ExAC AF: 0.304 AC: 36926

Asia WGS AF: 0.158 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	4.2	H
MutationTaster	Benign	1.0e-37	P;P;P
PrimateAI	Benign	0.33	T
Polyphen		0.98	D
ClinPred		0.055	T
GERP RS		5.4
Varity_R		0.72
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs7941731; hg19: chr11-4825225; COSMIC: COSV61888172;