rs10838881

Positions:

• chr11-48365723-T-C

Variant summary

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

The NM_001348223.2(OR4C5):​c.743A>G​(p.Lys248Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 702,978 control chromosomes in the GnomAD database, including 8,924 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2797 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6127 hom.)
• Consequence: OR4C5 NM_001348223.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

Genes affected

OR4C5 (HGNC:14702): (olfactory receptor family 4 subfamily C member 5) 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, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021905273).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4C5	NM_001348223.2	c.743A>G	p.Lys248Arg	missense_variant	1/1	ENST00000319813.3	NP_001335152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4C5	ENST00000319813.3	c.743A>G	p.Lys248Arg	missense_variant	1/1	6	NM_001348223.2	ENSP00000321338.3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26976 AN: 151964 Hom.: 2795 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.137

GnomAD3 exomes AF: 0.171 AC: 19240 AN: 112448 Hom.: 775 AF XY: 0.169 AC XY: 10283 AN XY: 60760

Gnomad AFR exome AF: 0.284

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.179

Gnomad SAS exome AF: 0.168

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.135

GnomAD4 exome AF: 0.142 AC: 78285 AN: 550894 Hom.: 6127 Cov.: 0 AF XY: 0.141 AC XY: 42108 AN XY: 298212

Gnomad4 AFR exome AF: 0.272

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.177 AC: 26988 AN: 152084 Hom.: 2797 Cov.: 32 AF XY: 0.179 AC XY: 13286 AN XY: 74338

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.134

Alfa AF: 0.138 Hom.: 2065

Bravo AF: 0.178

ExAC AF: 0.101 AC: 2379

Asia WGS AF: 0.137 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.75	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.19
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.027	D
Vest4		0.039
MPC		0.0057
ClinPred		0.022	T
GERP RS		4.3
Varity_R		0.25
gMVP		0.19

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: rs10838881; hg19: chr11-48387275; COSMIC: COSV60562465;