rs11421222

chr9-122629491-CA-Cchr9-122629491-CA-CAAchr9-122629491-CA-CAAAchr9-122629491-CA-CAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001004450.3(OR1B1):c.41del(p.Leu14CysfsTer24) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000686 in 1,457,436 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: OR1B1 NM_001004450.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75

Genes affected

OR1B1 (HGNC:8181): (olfactory receptor family 1 subfamily B member 1) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR1B1	NM_001004450.3	c.41del	p.Leu14CysfsTer24	frameshift_variant	2/2	ENST00000623530.2
LOC124902265	XR_007061759.1	n.345-7605del		intron_variant, non_coding_transcript_variant
OR1B1	NM_001409693.1	c.41del	p.Leu14CysfsTer24	frameshift_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR1B1	ENST00000623530.2	c.41del	p.Leu14CysfsTer24	frameshift_variant	2/2		NM_001004450.3	P1
	ENST00000431442.2	n.4768-7605del		intron_variant, non_coding_transcript_variant		3
OR1B1	ENST00000707075.1	c.41del	p.Leu14CysfsTer24	frameshift_variant	2/2			P1
	ENST00000419604.1	n.279-7608del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457436 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 724930

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11421222; hg19: chr9-125391770;