chr6-29397464-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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.

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.765T>C	p.Leu255Leu	synonymous	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.765T>C	p.Leu255Leu	synonymous	Exon 2 of 2	ENSP00000493463.1	P58182
	OR12D2	ENST00000623183.1	TSL:6	c.765T>C	p.Leu255Leu	synonymous	Exon 1 of 1	ENSP00000485112.1	P58182
	OR5V1	ENST00000377154.1	TSL:6	c.-83+25143A>G		intron	N/A	ENSP00000366359.1	Q9UGF6

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

GnomAD2 exomes AF: 0.396 AC: 97549 AN: 246498 AF XY: 0.393

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 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

African (AFR) AF: 0.229 AC: 7662 AN: 33468

American (AMR) AF: 0.400 AC: 17882 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 13080 AN: 26134

East Asian (EAS) AF: 0.346 AC: 13736 AN: 39698

South Asian (SAS) AF: 0.282 AC: 24348 AN: 86250

European-Finnish (FIN) AF: 0.417 AC: 21815 AN: 52310

Middle Eastern (MID) AF: 0.369 AC: 2130 AN: 5768

European-Non Finnish (NFE) AF: 0.437 AC: 485942 AN: 1111794

Other (OTH) AF: 0.409 AC: 24678 AN: 60372

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

African (AFR) AF: 0.237 AC: 9841 AN: 41490

American (AMR) AF: 0.388 AC: 5923 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1778 AN: 3470

East Asian (EAS) AF: 0.344 AC: 1777 AN: 5164

South Asian (SAS) AF: 0.264 AC: 1272 AN: 4812

European-Finnish (FIN) AF: 0.428 AC: 4514 AN: 10552

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29778 AN: 67946

Other (OTH) AF: 0.382 AC: 807 AN: 2110

Alfa AF: 0.419 Hom.: 15042

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.51
PhyloP100		-3.0
Mutation Taster		=100/0	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: rs2073150; hg19: chr6-29365241; COSMIC: COSV65826343;