9-122629491-CAA-CAAAAAAAAAAA

Variant names:

• chr9-122629491-C-CAAAAAAAAA
• rs11421222
• NM_001004450.3:c.41_42insTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001004450.3(OR1B1):​c.41_42insTTTTTTTTT​(p.Phe13_Leu14insPhePhePhe) variant causes a disruptive inframe insertion change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: OR1B1 NM_001004450.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• Publications: 17 publications found

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]

ENSG00000234156 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001004450.3.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004450.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1B1	NM_001004450.3	MANE Select	c.41_42insTTTTTTTTT	p.Phe13_Leu14insPhePhePhe	disruptive_inframe_insertion	Exon 2 of 2	NP_001004450.2
	OR1B1	NM_001409693.1		c.41_42insTTTTTTTTT	p.Phe13_Leu14insPhePhePhe	disruptive_inframe_insertion	Exon 2 of 2	NP_001396622.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1B1	ENST00000623530.2	TSL:6 MANE Select	c.41_42insTTTTTTTTT	p.Phe13_Leu14insPhePhePhe	disruptive_inframe_insertion	Exon 2 of 2	ENSP00000485577.2
	OR1B1	ENST00000707075.1		c.41_42insTTTTTTTTT	p.Phe13_Leu14insPhePhePhe	disruptive_inframe_insertion	Exon 2 of 2	ENSP00000516726.1
	ENSG00000234156	ENST00000419604.1	TSL:5	n.279-7608_279-7607insAAAAAAAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151594 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 245860 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151594 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 73982

African (AFR) AF: 0.00 AC: 0 AN: 41208

American (AMR) AF: 0.00 AC: 0 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67906

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.000427 Hom.: 1697

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7
Mutation Taster		=89/11	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11421222; hg19: chr9-125391770;