chr11-48365723-T-C

Variant names:

• chr11-48365723-T-C
• rs10838881
• NM_001348223.2:c.743A>G

Variant summary

Our verdict is Benign. The variant received -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. 11/18 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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OR4C5	NM_001348223.2	c.743A>G	p.Lys248Arg	missense_variant	Exon 1 of 1	ENST00000319813.3	NP_001335152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4C5	ENST00000319813.3	c.743A>G	p.Lys248Arg	missense_variant	Exon 1 of 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

GnomAD2 exomes AF: 0.171 AC: 19240 AN: 112448 AF XY: 0.169

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 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

African (AFR) AF: 0.272 AC: 4304 AN: 15804

American (AMR) AF: 0.133 AC: 4625 AN: 34714

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 2096 AN: 20030

East Asian (EAS) AF: 0.162 AC: 5187 AN: 32102

South Asian (SAS) AF: 0.149 AC: 9377 AN: 62774

European-Finnish (FIN) AF: 0.160 AC: 5399 AN: 33706

Middle Eastern (MID) AF: 0.107 AC: 437 AN: 4078

European-Non Finnish (NFE) AF: 0.135 AC: 42718 AN: 317030

Other (OTH) AF: 0.135 AC: 4142 AN: 30656

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

African (AFR) AF: 0.275 AC: 11392 AN: 41470

American (AMR) AF: 0.133 AC: 2036 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3468

East Asian (EAS) AF: 0.163 AC: 844 AN: 5174

South Asian (SAS) AF: 0.138 AC: 663 AN: 4812

European-Finnish (FIN) AF: 0.174 AC: 1842 AN: 10570

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9410 AN: 67988

Other (OTH) AF: 0.134 AC: 284 AN: 2114

Alfa AF: 0.147 Hom.: 5779

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
PhyloP100		1.9
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
Mutation Taster		=99/1	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: rs10838881; hg19: chr11-48387275; COSMIC: COSV60562465;