rs4489787

chr12-48417317-T-C

Variant summary

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

The ENST00000609970.1(OR8S21P):n.21A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,204 control chromosomes in the GnomAD database, including 835 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 0.10 (834 hom., cov: 32)
  • Exomes 𝑓: 0.25 (1 hom.)
• Consequence: OR8S21P ENST00000609970.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87

Genes affected

OR8S21P (HGNC:31317): (olfactory receptor family 8 subfamily S member 21 pseudogene) 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C12orf54	XM_011537896.3	c.-449+3735T>C		intron_variant
C12orf54	XM_017018796.2	c.-523+3735T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR8S21P	ENST00000609970.1	n.21A>G		non_coding_transcript_exon_variant	1/1
	ENST00000548257.1	n.238-24770T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15357 AN: 152054 Hom.: 833 Cov.: 32

Gnomad AFR AF: 0.0803

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0325

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.250 AC: 8 AN: 32 Hom.: 1 Cov.: 0 AF XY: 0.222 AC XY: 4 AN XY: 18

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.101 AC: 15356 AN: 152172 Hom.: 834 Cov.: 32 AF XY: 0.0987 AC XY: 7340 AN XY: 74390

Gnomad4 AFR AF: 0.0803

Gnomad4 AMR AF: 0.0952

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.0659

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.122

Alfa AF: 0.117 Hom.: 2305

Bravo AF: 0.0987

Asia WGS AF: 0.0590 AC: 204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.079
Dann	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4489787; hg19: chr12-48811100;