chr12-48560149-G-T

Variant names:

• chr12-48560149-G-T
• rs17237198
• NM_001396061.1:c.268G>T

Variant summary

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

The NM_001396061.1(OR5BS1):​c.268G>T​(p.Glu90*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000401 in 249,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: OR5BS1 NM_001396061.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR5BS1	NM_001396061.1	c.268G>T	p.Glu90*	stop_gained	Exon 1 of 2	ENST00000328207.6	NP_001382990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR5BS1P	ENST00000328207.6	c.268G>T	p.Glu90*	stop_gained	Exon 1 of 2	6	NM_001396061.1	ENSP00000494254.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000401 AC: 1 AN: 249228 Hom.: 0 Cov.: 0 AF XY: 0.00000792 AC XY: 1 AN XY: 126296

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7258

American (AMR) AF: 0.00 AC: 0 AN: 7446

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 22894

South Asian (SAS) AF: 0.00 AC: 0 AN: 3128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2928

European-Non Finnish (NFE) AF: 0.00000632 AC: 1 AN: 158316

Other (OTH) AF: 0.00 AC: 0 AN: 16654

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Pathogenic	35
DANN	Benign	0.63
FATHMM_MKL	Benign	0.063	N
PhyloP100		1.9
GERP RS		4.3
PromoterAI		-0.015	Neutral

Splicing

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

Other links and lift over

dbSNP: rs17237198; hg19: chr12-48953932;