12-48560442-G-C

Position:

• chr12-48560442-G-C

Variant summary

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

The NM_001396061.1(OR5BS1P):​c.561G>C​(p.Leu187Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 401,242 control chromosomes in the GnomAD database, including 47,737 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 0.41 (15206 hom., cov: 31)
  • Exomes 𝑓: 0.50 (32531 hom.)
• Consequence: OR5BS1P NM_001396061.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=5.4365396E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5BS1P	NM_001396061.1	c.561G>C	p.Leu187Phe	missense_variant	1/2	ENST00000328207.6	NP_001382990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5BS1P	ENST00000328207.6	c.561G>C	p.Leu187Phe	missense_variant	1/2	6	NM_001396061.1	ENSP00000494254.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62350 AN: 151814 Hom.: 15201 Cov.: 31

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.498 AC: 124132 AN: 249310 Hom.: 32531 Cov.: 0 AF XY: 0.502 AC XY: 63412 AN XY: 126382

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.483

Gnomad4 ASJ exome AF: 0.505

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.387

Gnomad4 FIN exome AF: 0.516

Gnomad4 NFE exome AF: 0.549

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.411 AC: 62374 AN: 151932 Hom.: 15206 Cov.: 31 AF XY: 0.410 AC XY: 30407 AN XY: 74230

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.439

Alfa AF: 0.473 Hom.: 2309

Bravo AF: 0.396

TwinsUK AF: 0.548 AC: 2033

ALSPAC AF: 0.557 AC: 2145

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_noAF	Benign	-0.74
CADD	Benign	20
DANN	Benign	0.70
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.00054	T
GERP RS		2.4
gMVP		0.027

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7312017; hg19: chr12-48954225; COSMIC: COSV60248349;