6-29397058-T-G

Variant names:

• chr6-29397058-T-G
• rs2073153
• NM_013936.4:c.359T>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.359T>G​(p.Leu120Arg) variant causes a missense change. The variant allele was found at a frequency of 0.41 in 1,612,102 control chromosomes in the GnomAD database, including 139,713 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 (10549 hom., cov: 32)
  • Exomes 𝑓: 0.42 (129164 hom.)
• Consequence: OR12D2 NM_013936.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.15
• Publications: 25 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=1.5491247E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR12D2	NM_013936.4	MANE Select	c.359T>G	p.Leu120Arg	missense	Exon 2 of 2	NP_039224.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR12D2	ENST00000642051.1	MANE Select	c.359T>G	p.Leu120Arg	missense	Exon 2 of 2	ENSP00000493463.1
	OR12D2	ENST00000623183.1	TSL:6	c.359T>G	p.Leu120Arg	missense	Exon 1 of 1	ENSP00000485112.1
	OR5V1	ENST00000377154.1	TSL:6	c.-83+25549A>C		intron	N/A	ENSP00000366359.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54450 AN: 151892 Hom.: 10542 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.376

GnomAD2 exomes AF: 0.390 AC: 96109 AN: 246188 AF XY: 0.388

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.392

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.325

Gnomad FIN exome AF: 0.420

Gnomad NFE exome AF: 0.441

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.416 AC: 607230 AN: 1460092 Hom.: 129164 Cov.: 44 AF XY: 0.414 AC XY: 300599 AN XY: 726408

African (AFR) AF: 0.197 AC: 6598 AN: 33472

American (AMR) AF: 0.389 AC: 17381 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 12682 AN: 26122

East Asian (EAS) AF: 0.346 AC: 13731 AN: 39692

South Asian (SAS) AF: 0.281 AC: 24266 AN: 86242

European-Finnish (FIN) AF: 0.418 AC: 21899 AN: 52418

Middle Eastern (MID) AF: 0.360 AC: 2075 AN: 5766

European-Non Finnish (NFE) AF: 0.436 AC: 484269 AN: 1111316

Other (OTH) AF: 0.403 AC: 24329 AN: 60364

GnomAD4 genome AF: 0.358 AC: 54462 AN: 152010 Hom.: 10549 Cov.: 32 AF XY: 0.359 AC XY: 26635 AN XY: 74288

African (AFR) AF: 0.204 AC: 8474 AN: 41482

American (AMR) AF: 0.371 AC: 5669 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1716 AN: 3462

East Asian (EAS) AF: 0.344 AC: 1779 AN: 5168

South Asian (SAS) AF: 0.263 AC: 1265 AN: 4812

European-Finnish (FIN) AF: 0.428 AC: 4522 AN: 10568

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

European-Non Finnish (NFE) AF: 0.437 AC: 29661 AN: 67932

Other (OTH) AF: 0.372 AC: 785 AN: 2112

Alfa AF: 0.396 Hom.: 16480

Bravo AF: 0.351

TwinsUK AF: 0.409 AC: 1516

ALSPAC AF: 0.437 AC: 1686

ESP6500AA AF: 0.221 AC: 669

ESP6500EA AF: 0.445 AC: 2409

ExAC AF: 0.384 AC: 45416

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	0.040
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.1
DANN	Benign	0.45
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.00015	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-4.0	N
PhyloP100		5.1
PrimateAI	Benign	0.16	T
Polyphen		0.0	B
ClinPred		0.0040	T
GERP RS		3.0
Varity_R		0.13
gMVP		0.36
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: rs2073153; hg19: chr6-29364835; COSMIC: COSV65826213;