6-29397464-T-C

Variant names:

• chr6-29397464-T-C
• rs2073150
• NM_013936.4:c.765T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_013936.4(OR12D2):​c.765T>C​(p.Leu255Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,612,520 control chromosomes in the GnomAD database, including 141,577 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (11021 hom., cov: 32)
  • Exomes 𝑓: 0.42 (130556 hom.)
• Consequence: OR12D2 NM_013936.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-2.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR12D2	NM_013936.4	c.765T>C	p.Leu255Leu	synonymous_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.765T>C	p.Leu255Leu	synonymous_variant	Exon 2 of 2		NM_013936.4	ENSP00000493463.1
OR12D2	ENST00000623183.1	c.765T>C	p.Leu255Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000485112.1
OR5V1	ENST00000377154.1	c.-83+25143A>G		intron_variant	Intron 3 of 3	6		ENSP00000366359.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56263 AN: 151894 Hom.: 11012 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.386

GnomAD3 exomes AF: 0.396 AC: 97549 AN: 246498 Hom.: 20120 AF XY: 0.393 AC XY: 52755 AN XY: 134326

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.404

Gnomad ASJ exome AF: 0.500

Gnomad EAS exome AF: 0.326

Gnomad SAS exome AF: 0.283

Gnomad FIN exome AF: 0.420

Gnomad NFE exome AF: 0.443

Gnomad OTH exome AF: 0.412

GnomAD4 exome AF: 0.419 AC: 611273 AN: 1460508 Hom.: 130556 Cov.: 55 AF XY: 0.416 AC XY: 302547 AN XY: 726598

Gnomad4 AFR exome AF: 0.229

Gnomad4 AMR exome AF: 0.400

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.346

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.437

Gnomad4 OTH exome AF: 0.409

GnomAD4 genome AF: 0.370 AC: 56288 AN: 152012 Hom.: 11021 Cov.: 32 AF XY: 0.370 AC XY: 27485 AN XY: 74286

Gnomad4 AFR AF: 0.237

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.382

Alfa AF: 0.420 Hom.: 12397

Bravo AF: 0.365

Asia WGS AF: 0.256 AC: 893 AN: 3478

EpiCase AF: 0.434

EpiControl AF: 0.444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.51

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: rs2073150; hg19: chr6-29365241; COSMIC: COSV65826343;