rs17237198

Positions:

• chr12-48560149-G-A

Variant summary

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

The NM_001396061.1(OR5BS1P):​c.268G>A​(p.Glu90Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 401,402 control chromosomes in the GnomAD database, including 1,490 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/8 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 0.082 (532 hom., cov: 32)
  • Exomes 𝑓: 0.084 (958 hom.)
• Consequence: OR5BS1P NM_001396061.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

Genes affected

OR5BS1P (HGNC:19627): (olfactory receptor family 5 subfamily BS member 1 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029495358).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR5BS1P	NM_001396061.1	c.268G>A	p.Glu90Lys	missense_variant	1/2	ENST00000328207.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR5BS1P	ENST00000328207.6	c.268G>A	p.Glu90Lys	missense_variant	1/2		NM_001396061.1	P1

Frequencies

GnomAD3 genomes AF: 0.0823 AC: 12513 AN: 152058 Hom.: 531 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0976

Gnomad EAS AF: 0.0295

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.0846

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.0967

GnomAD4 exome AF: 0.0845 AC: 21056 AN: 249226 Hom.: 958 Cov.: 0 AF XY: 0.0853 AC XY: 10770 AN XY: 126294

Gnomad4 AFR exome AF: 0.0738

Gnomad4 AMR exome AF: 0.0670

Gnomad4 ASJ exome AF: 0.0873

Gnomad4 EAS exome AF: 0.0228

Gnomad4 SAS exome AF: 0.0483

Gnomad4 FIN exome AF: 0.0870

Gnomad4 NFE exome AF: 0.0937

Gnomad4 OTH exome AF: 0.0848

GnomAD4 genome AF: 0.0823 AC: 12518 AN: 152176 Hom.: 532 Cov.: 32 AF XY: 0.0800 AC XY: 5947 AN XY: 74378

Gnomad4 AFR AF: 0.0720

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0976

Gnomad4 EAS AF: 0.0295

Gnomad4 SAS AF: 0.0560

Gnomad4 FIN AF: 0.0846

Gnomad4 NFE AF: 0.0947

Gnomad4 OTH AF: 0.0947

Alfa AF: 0.0865 Hom.: 211

Bravo AF: 0.0805

TwinsUK AF: 0.0939 AC: 348

ALSPAC AF: 0.0937 AC: 361

Asia WGS AF: 0.0450 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.57
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0029	T
GERP RS		4.3
gMVP		0.055

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17237198; hg19: chr12-48953932;