rs2073152

Positions:

• chr6-29397061-C-G
• chr6-29397061-C-T

Variant summary

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

The NM_013936.4(OR12D2):​c.362C>G​(p.Ser121Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,612,350 control chromosomes in the GnomAD database, including 56,985 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.22 (4151 hom., cov: 32)
  • Exomes 𝑓: 0.26 (52834 hom.)
• Consequence: OR12D2 NM_013936.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

Genes affected

OR12D2 (HGNC:8178): (olfactory receptor family 12 subfamily D 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. 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]

OR5V1 (HGNC:13972): (olfactory receptor family 5 subfamily V 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014755636).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR12D2	NM_013936.4	c.362C>G	p.Ser121Cys	missense_variant	2/2	ENST00000642051.1	NP_039224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR12D2	ENST00000642051.1	c.362C>G	p.Ser121Cys	missense_variant	2/2		NM_013936.4	ENSP00000493463.1
OR12D2	ENST00000623183.1	c.362C>G	p.Ser121Cys	missense_variant	1/1	6		ENSP00000485112.1
OR5V1	ENST00000377154.1	c.-83+25546G>C		intron_variant		6		ENSP00000366359.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33788 AN: 152016 Hom.: 4153 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.230

GnomAD3 exomes AF: 0.231 AC: 56777 AN: 246238 Hom.: 7343 AF XY: 0.229 AC XY: 30749 AN XY: 134184

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.323

Gnomad EAS exome AF: 0.228

Gnomad SAS exome AF: 0.116

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.285

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.263 AC: 383956 AN: 1460216 Hom.: 52834 Cov.: 46 AF XY: 0.260 AC XY: 188665 AN XY: 726464

Gnomad4 AFR exome AF: 0.115

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.320

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.222 AC: 33790 AN: 152134 Hom.: 4151 Cov.: 32 AF XY: 0.221 AC XY: 16428 AN XY: 74362

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.227

Alfa AF: 0.272 Hom.: 1947

Bravo AF: 0.211

TwinsUK AF: 0.261 AC: 966

ALSPAC AF: 0.280 AC: 1080

ESP6500AA AF: 0.132 AC: 400

ESP6500EA AF: 0.293 AC: 1588

ExAC AF: 0.229 AC: 27063

Asia WGS AF: 0.123 AC: 428 AN: 3478

EpiCase AF: 0.278

EpiControl AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.6
DANN	Benign	0.83
DEOGEN2	Benign	0.0012	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.36	.;T
MetaRNN	Benign	0.015	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.38	N;N
PrimateAI	Benign	0.20	T
Polyphen		0.099	B;B
ClinPred		0.0066	T
GERP RS		1.4
Varity_R		0.095
gMVP		0.20

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: rs2073152; hg19: chr6-29364838; COSMIC: COSV65828190;