6-29397061-C-G

Variant names:

• chr6-29397061-C-G
• rs2073152
• NM_013936.4:c.362C>G

Variant summary

Our verdict is Benign. The variant received -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. 13/18 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 0.22 (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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OR12D2	NM_013936.4	c.362C>G	p.Ser121Cys	missense_variant	Exon 2 of 2	ENST00000642051.1	NP_039224.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR12D2	ENST00000642051.1	c.362C>G	p.Ser121Cys	missense_variant	Exon 2 of 2		NM_013936.4	ENSP00000493463.1
OR12D2	ENST00000623183.1	c.362C>G	p.Ser121Cys	missense_variant	Exon 1 of 1	6		ENSP00000485112.1
OR5V1	ENST00000377154.1	c.-83+25546G>C		intron_variant	Intron 3 of 3	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

GnomAD2 exomes AF: 0.231 AC: 56777 AN: 246238 AF XY: 0.229

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 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

African (AFR) AF: 0.115 AC: 3839 AN: 33472

American (AMR) AF: 0.150 AC: 6728 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 8356 AN: 26126

East Asian (EAS) AF: 0.214 AC: 8491 AN: 39696

South Asian (SAS) AF: 0.116 AC: 10004 AN: 86250

European-Finnish (FIN) AF: 0.284 AC: 14859 AN: 52412

Middle Eastern (MID) AF: 0.209 AC: 1205 AN: 5766

European-Non Finnish (NFE) AF: 0.283 AC: 315066 AN: 1111410

Other (OTH) AF: 0.255 AC: 15408 AN: 60370

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

African (AFR) AF: 0.119 AC: 4962 AN: 41528

American (AMR) AF: 0.191 AC: 2915 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1170 AN: 3464

East Asian (EAS) AF: 0.227 AC: 1174 AN: 5178

South Asian (SAS) AF: 0.103 AC: 499 AN: 4828

European-Finnish (FIN) AF: 0.285 AC: 3018 AN: 10586

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19184 AN: 67954

Other (OTH) AF: 0.227 AC: 479 AN: 2110

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
PhyloP100		0.074
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
Mutation Taster		=100/0	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: rs2073152; hg19: chr6-29364838; COSMIC: COSV65828190;