11-4804297-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001005177.3(OR52R1):c.84G>A(p.Leu28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,614,040 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0045 (30 hom.)
• Consequence: OR52R1 NM_001005177.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.574

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-4804297-C-T is Benign according to our data. Variant chr11-4804297-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2641534.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.574 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR52R1	NM_001005177.3	c.84G>A	p.Leu28=	synonymous_variant	1/1	ENST00000624978.1
MMP26	NM_021801.5	c.-145+36956C>T		intron_variant		ENST00000380390.6
MMP26	NM_001384608.1	c.-153+36956C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR52R1	ENST00000624978.1	c.84G>A	p.Leu28=	synonymous_variant	1/1		NM_001005177.3	P1
MMP26	ENST00000380390.6	c.-145+36956C>T		intron_variant		5	NM_021801.5	P1
MMP26	ENST00000300762.2	c.-153+36956C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00439 AC: 667 AN: 152092 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00584

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00340 AC: 853 AN: 251180 Hom.: 4 AF XY: 0.00320 AC XY: 435 AN XY: 135748

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00452

Gnomad ASJ exome AF: 0.00367

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.000739

Gnomad NFE exome AF: 0.00515

Gnomad OTH exome AF: 0.00604

GnomAD4 exome AF: 0.00453 AC: 6616 AN: 1461830 Hom.: 30 Cov.: 33 AF XY: 0.00440 AC XY: 3199 AN XY: 727210

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00492

Gnomad4 ASJ exome AF: 0.00337

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.000786

Gnomad4 NFE exome AF: 0.00529

Gnomad4 OTH exome AF: 0.00497

GnomAD4 genome AF: 0.00438 AC: 667 AN: 152210 Hom.: 4 Cov.: 31 AF XY: 0.00396 AC XY: 295 AN XY: 74422

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00584

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00517 Hom.: 3

Bravo AF: 0.00514

EpiCase AF: 0.00573

EpiControl AF: 0.00634

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, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.23
Dann	Benign	0.82

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: rs117852117; hg19: chr11-4825527;