12-48560442-G-T

Variant names:

• chr12-48560442-G-T
• rs7312017
• NM_001396061.1:c.561G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001396061.1(OR5BS1):​c.561G>T​(p.Leu187Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR5BS1 NM_001396061.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 7 publications found

Genes affected

OR5BS1 (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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1281004).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396061.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5BS1	NM_001396061.1	MANE Select	c.561G>T	p.Leu187Phe	missense	Exon 1 of 2	NP_001382990.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5BS1P	ENST00000328207.6	TSL:6 MANE Select	c.561G>T	p.Leu187Phe	missense	Exon 1 of 2	ENSP00000494254.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 249316 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 126384

African (AFR) AF: 0.00 AC: 0 AN: 7254

American (AMR) AF: 0.00 AC: 0 AN: 7444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9244

East Asian (EAS) AF: 0.00 AC: 0 AN: 22896

South Asian (SAS) AF: 0.00 AC: 0 AN: 3122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2930

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158442

Other (OTH) AF: 0.00 AC: 0 AN: 16640

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_noAF	Benign	-0.74
CADD	Benign	20
DANN	Benign	0.81
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.13	T
PhyloP100		-1.1
GERP RS		2.4
gMVP		0.027

Splicing

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

Other links and lift over

dbSNP: rs7312017; hg19: chr12-48954225; COSMIC: COSV60248196;