NM_013936.4:c.167T>C

Variant names:

• chr6-29396866-T-C
• rs4987411
• NM_013936.4:c.167T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013936.4(OR12D2):​c.167T>C​(p.Leu56Pro) variant causes a missense change. The variant allele was found at a frequency of 0.41 in 1,608,974 control chromosomes in the GnomAD database, including 139,668 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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 0.36 (10557 hom., cov: 31)
  • Exomes 𝑓: 0.42 (129111 hom.)
• Consequence: OR12D2 NM_013936.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54
• Publications: 24 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=0.0018766224).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013936.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR12D2	NM_013936.4	MANE Select	c.167T>C	p.Leu56Pro	missense	Exon 2 of 2	NP_039224.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR12D2	ENST00000642051.1	MANE Select	c.167T>C	p.Leu56Pro	missense	Exon 2 of 2	ENSP00000493463.1
	OR12D2	ENST00000623183.1	TSL:6	c.167T>C	p.Leu56Pro	missense	Exon 1 of 1	ENSP00000485112.1
	OR5V1	ENST00000377154.1	TSL:6	c.-83+25741A>G		intron	N/A	ENSP00000366359.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54456 AN: 151874 Hom.: 10550 Cov.: 31

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.391 AC: 96210 AN: 246284 AF XY: 0.389

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.393

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.326

Gnomad FIN exome AF: 0.420

Gnomad NFE exome AF: 0.441

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.416 AC: 605613 AN: 1456982 Hom.: 129111 Cov.: 40 AF XY: 0.414 AC XY: 299868 AN XY: 725008

African (AFR) AF: 0.196 AC: 6559 AN: 33400

American (AMR) AF: 0.389 AC: 17395 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 12673 AN: 26106

East Asian (EAS) AF: 0.346 AC: 13730 AN: 39686

South Asian (SAS) AF: 0.281 AC: 24229 AN: 86168

European-Finnish (FIN) AF: 0.417 AC: 21814 AN: 52306

Middle Eastern (MID) AF: 0.360 AC: 2071 AN: 5760

European-Non Finnish (NFE) AF: 0.436 AC: 482860 AN: 1108570

Other (OTH) AF: 0.403 AC: 24282 AN: 60272

GnomAD4 genome AF: 0.358 AC: 54468 AN: 151992 Hom.: 10557 Cov.: 31 AF XY: 0.359 AC XY: 26637 AN XY: 74282

African (AFR) AF: 0.204 AC: 8469 AN: 41478

American (AMR) AF: 0.371 AC: 5671 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1720 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1768 AN: 5146

South Asian (SAS) AF: 0.264 AC: 1269 AN: 4808

European-Finnish (FIN) AF: 0.428 AC: 4522 AN: 10564

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29671 AN: 67928

Other (OTH) AF: 0.371 AC: 784 AN: 2112

Alfa AF: 0.396 Hom.: 18366

Bravo AF: 0.351

TwinsUK AF: 0.417 AC: 1545

ALSPAC AF: 0.442 AC: 1705

ESP6500AA AF: 0.220 AC: 663

ESP6500EA AF: 0.444 AC: 2407

ExAC AF: 0.383 AC: 45073

Asia WGS AF: 0.255 AC: 889 AN: 3478

EpiCase AF: 0.432

EpiControl AF: 0.441

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.036
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.54
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-3.4	N
PhyloP100		5.5
PrimateAI	Benign	0.28	T
Polyphen		0.0	B
ClinPred		0.0034	T
GERP RS		3.2
PromoterAI		-0.00090	Neutral
Varity_R		0.18
gMVP		0.23
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4987411; hg19: chr6-29364643; COSMIC: COSV65826428;