11-4804300-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001005177.3(OR52R1):c.81G>C(p.Gln27His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,614,068 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00094 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: OR52R1 NM_001005177.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.89

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0053685308).
• BP6: Variant 11-4804300-C-G is Benign according to our data. Variant chr11-4804300-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2641535.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR52R1	NM_001005177.3	c.81G>C	p.Gln27His	missense_variant	1/1	ENST00000624978.1
MMP26	NM_021801.5	c.-145+36959C>G		intron_variant		ENST00000380390.6
MMP26	NM_001384608.1	c.-153+36959C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR52R1	ENST00000624978.1	c.81G>C	p.Gln27His	missense_variant	1/1		NM_001005177.3	P1
MMP26	ENST00000380390.6	c.-145+36959C>G		intron_variant		5	NM_021801.5	P1
MMP26	ENST00000300762.2	c.-153+36959C>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.000940 AC: 143 AN: 152106 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00168

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00143 AC: 359 AN: 251204 Hom.: 1 AF XY: 0.00124 AC XY: 168 AN XY: 135762

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00134

Gnomad NFE exome AF: 0.00272

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.00158 AC: 2308 AN: 1461844 Hom.: 5 Cov.: 33 AF XY: 0.00152 AC XY: 1107 AN XY: 727214

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00144

Gnomad4 NFE exome AF: 0.00191

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.000939 AC: 143 AN: 152224 Hom.: 0 Cov.: 31 AF XY: 0.000873 AC XY: 65 AN XY: 74428

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00168

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00103 Hom.: 0

Bravo AF: 0.000782

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.00207 AC: 251

EpiCase AF: 0.00136

EpiControl AF: 0.00148

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

OR52R1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.0010
Dann	Benign	0.50
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.0054	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	-0.055	N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.23	T
Polyphen		0.0050	B
ClinPred		0.031	T
GERP RS		-11
Varity_R		0.049
gMVP		0.48

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: rs61746977; hg19: chr11-4825530;