6-29396838-G-T

Variant names:

• chr6-29396838-G-T
• rs9257834
• NM_013936.4:c.139G>T

Variant summary

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

The NM_013936.4(OR12D2):​c.139G>T​(p.Val47Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,609,628 control chromosomes in the GnomAD database, including 139,694 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 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 (10560 hom., cov: 31)
  • Exomes 𝑓: 0.42 (129134 hom.)
• Consequence: OR12D2 NM_013936.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 39 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=5.995035E-4).
• 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.139G>T	p.Val47Phe	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.139G>T	p.Val47Phe	missense	Exon 2 of 2	ENSP00000493463.1
	OR12D2	ENST00000623183.1	TSL:6	c.139G>T	p.Val47Phe	missense	Exon 1 of 1	ENSP00000485112.1
	OR5V1	ENST00000377154.1	TSL:6	c.-83+25769C>A		intron	N/A	ENSP00000366359.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54465 AN: 151828 Hom.: 10553 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: 0.264

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.391 AC: 96250 AN: 246362 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: 605985 AN: 1457682 Hom.: 129134 Cov.: 40 AF XY: 0.414 AC XY: 300030 AN XY: 725308

African (AFR) AF: 0.196 AC: 6566 AN: 33416

American (AMR) AF: 0.389 AC: 17391 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 12677 AN: 26112

East Asian (EAS) AF: 0.346 AC: 13729 AN: 39684

South Asian (SAS) AF: 0.281 AC: 24242 AN: 86194

European-Finnish (FIN) AF: 0.417 AC: 21812 AN: 52306

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

European-Non Finnish (NFE) AF: 0.436 AC: 483212 AN: 1109226

Other (OTH) AF: 0.403 AC: 24281 AN: 60270

GnomAD4 genome AF: 0.359 AC: 54477 AN: 151946 Hom.: 10560 Cov.: 31 AF XY: 0.359 AC XY: 26653 AN XY: 74270

African (AFR) AF: 0.205 AC: 8476 AN: 41442

American (AMR) AF: 0.371 AC: 5678 AN: 15290

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

East Asian (EAS) AF: 0.344 AC: 1765 AN: 5136

South Asian (SAS) AF: 0.264 AC: 1273 AN: 4824

European-Finnish (FIN) AF: 0.429 AC: 4532 AN: 10562

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

European-Non Finnish (NFE) AF: 0.437 AC: 29655 AN: 67906

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

Alfa AF: 0.401 Hom.: 29390

Bravo AF: 0.351

TwinsUK AF: 0.417 AC: 1545

ALSPAC AF: 0.442 AC: 1705

ESP6500AA AF: 0.221 AC: 668

ESP6500EA AF: 0.445 AC: 2411

ExAC AF: 0.383 AC: 45029

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	0.12
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.00060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.11
PrimateAI	Benign	0.30	T
Polyphen		0.99	D
ClinPred		0.037	T
GERP RS		3.2
PromoterAI		0.0026	Neutral
Varity_R		0.35
gMVP		0.46
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: rs9257834; hg19: chr6-29364615; COSMIC: COSV65828180;