rs10500626

Positions:

• chr11-4916649-C-T

Variant summary

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

The NM_001005238.2(OR51G2):​c.-76-910G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 152,188 control chromosomes in the GnomAD database, including 846 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 0.093 (846 hom., cov: 32)
• Consequence: OR51G2 NM_001005238.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

Genes affected

OR51G2 (HGNC:15198): (olfactory receptor family 51 subfamily G member 2) 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. [provided by RefSeq, Jul 2008]

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 (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR51G2	NM_001005238.2	c.-76-910G>A		intron_variant		ENST00000641926.1	NP_001005238.1
MMP26	NM_021801.5	c.-144-71419C>T		intron_variant		ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-152-71621C>T		intron_variant			NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR51G2	ENST00000641926.1	c.-76-910G>A		intron_variant			NM_001005238.2	ENSP00000493323.1
MMP26	ENST00000380390.6	c.-144-71419C>T		intron_variant		5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-152-71621C>T		intron_variant		1		ENSP00000300762.2

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14165 AN: 152070 Hom.: 847 Cov.: 32

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0282

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.114

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0931 AC: 14162 AN: 152188 Hom.: 846 Cov.: 32 AF XY: 0.0928 AC XY: 6903 AN XY: 74404

Gnomad4 AFR AF: 0.0327

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.113

Alfa AF: 0.103 Hom.: 142

Bravo AF: 0.0884

Asia WGS AF: 0.0170 AC: 61 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.61

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: rs10500626; hg19: chr11-4937879;