chr6-29396866-T-C

Position:

• chr6-29396866-T-C

Variant summary

Our verdict is Benign. Variant got -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. 11/17 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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=0.0018766224).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR12D2	NM_013936.4	c.167T>C	p.Leu56Pro	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.167T>C	p.Leu56Pro	missense_variant	2/2		NM_013936.4	ENSP00000493463.1
OR12D2	ENST00000623183.1	c.167T>C	p.Leu56Pro	missense_variant	1/1	6		ENSP00000485112.1
OR5V1	ENST00000377154.1	c.-83+25741A>G		intron_variant		6		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

GnomAD3 exomes AF: 0.391 AC: 96210 AN: 246284 Hom.: 19675 AF XY: 0.389 AC XY: 52165 AN XY: 134244

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 SAS exome AF: 0.282

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

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.281

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.403

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

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.371

Alfa AF: 0.412 Hom.: 12135

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 v4.3

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;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;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-3.4	N;N
PrimateAI	Benign	0.28	T
Polyphen		0.0	B;B
ClinPred		0.0034	T
GERP RS		3.2
Varity_R		0.18
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs4987411; hg19: chr6-29364643; COSMIC: COSV65826428;