rs7941731

Variant names:

• chr11-4803995-A-G
• rs7941731
• NM_001005177.3:c.386T>C

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005177.3. 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
	OR52R1	NM_001005177.3	MANE Select	c.386T>C	p.Ile129Thr	missense	Exon 1 of 1	NP_001005177.3	Q8NGF1
	MMP26	NM_021801.5	MANE Select	c.-145+36654A>G		intron	N/A	NP_068573.2	Q9NRE1
	MMP26	NM_001384608.1		c.-153+36654A>G		intron	N/A	NP_001371537.1	A0A8J8YUH5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52R1	ENST00000624978.1	TSL:6 MANE Select	c.386T>C	p.Ile129Thr	missense	Exon 1 of 1	ENSP00000485292.1	Q8NGF1
	MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-145+36654A>G		intron	N/A	ENSP00000369753.1	Q9NRE1
	MMP26	ENST00000300762.2	TSL:1	c.-153+36654A>G		intron	N/A	ENSP00000300762.2	A0A8J8YUH5

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

GnomAD2 exomes AF: 0.298 AC: 74801 AN: 250864 AF XY: 0.301

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 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

African (AFR) AF: 0.527 AC: 17659 AN: 33478

American (AMR) AF: 0.211 AC: 9437 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 13818 AN: 26136

East Asian (EAS) AF: 0.0217 AC: 860 AN: 39696

South Asian (SAS) AF: 0.253 AC: 21836 AN: 86258

European-Finnish (FIN) AF: 0.264 AC: 14077 AN: 53368

Middle Eastern (MID) AF: 0.489 AC: 2821 AN: 5768

European-Non Finnish (NFE) AF: 0.333 AC: 370077 AN: 1111964

Other (OTH) AF: 0.346 AC: 20919 AN: 60394

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

African (AFR) AF: 0.513 AC: 21124 AN: 41176

American (AMR) AF: 0.298 AC: 4524 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1859 AN: 3460

East Asian (EAS) AF: 0.0196 AC: 101 AN: 5160

South Asian (SAS) AF: 0.250 AC: 1195 AN: 4784

European-Finnish (FIN) AF: 0.258 AC: 2707 AN: 10500

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22697 AN: 67880

Other (OTH) AF: 0.410 AC: 858 AN: 2092

Alfa AF: 0.351 Hom.: 38994

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 v4.9

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
PhyloP100		9.2
PrimateAI	Benign	0.33	T
Polyphen		0.98	D
ClinPred		0.055	T
GERP RS		5.4
PromoterAI		0.0015	Neutral
Varity_R		0.72
gMVP		0.37
Mutation Taster		=67/33	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7941731; hg19: chr11-4825225; COSMIC: COSV61888172;