rs7753474

Positions:

• chr6-29373531-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030959.3(OR12D3):​c.*806C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,512 control chromosomes in the GnomAD database, including 3,901 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 0.22 (3889 hom., cov: 32)
  • Exomes 𝑓: 0.20 (12 hom.)
• Consequence: OR12D3 NM_030959.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647

Genes affected

OR12D3 (HGNC:13963): (olfactory receptor family 12 subfamily D member 3) 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]

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 (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR12D3	NM_030959.3	c.*806C>T		3_prime_UTR_variant	1/1	ENST00000396806.3	NP_112221.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR12D3	ENST00000396806.3	c.*806C>T		3_prime_UTR_variant	1/1		NM_030959.3	ENSP00000380023	P1
OR5V1	ENST00000377154.1	c.-82-17254C>T		intron_variant				ENSP00000366359	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33869 AN: 151850 Hom.: 3883 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.202 AC: 110 AN: 544 Hom.: 12 Cov.: 0 AF XY: 0.232 AC XY: 64 AN XY: 276

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.545

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.223 AC: 33894 AN: 151968 Hom.: 3889 Cov.: 32 AF XY: 0.225 AC XY: 16681 AN XY: 74250

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.232

Alfa AF: 0.199 Hom.: 5104

Bravo AF: 0.230

Asia WGS AF: 0.251 AC: 870 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.82
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs7753474; hg19: chr6-29341308;