9-122629491-CAA-CAAA

Variant names:

• chr9-122629491-C-CA
• rs11421222
• ENST00000623530.2:c.41dupT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001004450.3(OR1B1):​c.41dupT​(p.Leu14PhefsTer9) variant causes a frameshift change. The variant allele was found at a frequency of 0.49 in 1,608,368 control chromosomes in the GnomAD database, including 196,273 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16793 hom., cov: 0)
  • Exomes 𝑓: 0.49 (179480 hom.)
• Consequence: OR1B1 NM_001004450.3 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

ENSG00000234156 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-122629491-C-CA is Benign according to our data. Variant chr9-122629491-C-CA is described in ClinVar as [Benign]. Clinvar id is 403271.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR1B1	NM_001004450.3	c.41dupT	p.Leu14PhefsTer9	frameshift_variant	Exon 2 of 2		NP_001004450.2
OR1B1	NM_001409693.1	c.41dupT	p.Leu14PhefsTer9	frameshift_variant	Exon 2 of 2		NP_001396622.1
LOC124902265	XR_007061759.1	n.345-7605dupA		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR1B1	ENST00000623530.2	c.41dupT	p.Leu14PhefsTer9	frameshift_variant	Exon 2 of 2	6		ENSP00000485577.2
OR1B1	ENST00000707075.1	c.41dupT	p.Leu14PhefsTer9	frameshift_variant	Exon 2 of 2			ENSP00000516726.1
ENSG00000234156	ENST00000419604.1	n.279-7608dupA		intron_variant	Intron 2 of 3	5
ENSG00000234156	ENST00000431442.2	n.4768-7605dupA		intron_variant	Intron 8 of 9	3

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70306 AN: 151482 Hom.: 16788 Cov.: 0

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.434

GnomAD3 exomes AF: 0.452 AC: 111099 AN: 245860 Hom.: 26307 AF XY: 0.460 AC XY: 61192 AN XY: 132972

Gnomad AFR exome AF: 0.422

Gnomad AMR exome AF: 0.271

Gnomad ASJ exome AF: 0.431

Gnomad EAS exome AF: 0.322

Gnomad SAS exome AF: 0.448

Gnomad FIN exome AF: 0.595

Gnomad NFE exome AF: 0.508

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.492 AC: 717437 AN: 1456768 Hom.: 179480 Cov.: 34 AF XY: 0.492 AC XY: 356417 AN XY: 724636

Gnomad4 AFR exome AF: 0.416

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.338

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.584

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.464 AC: 70337 AN: 151600 Hom.: 16793 Cov.: 0 AF XY: 0.468 AC XY: 34625 AN XY: 74060

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.435

Alfa AF: 0.381 Hom.: 1697

Asia WGS AF: 0.381 AC: 1329 AN: 3478

EpiCase AF: 0.492

EpiControl AF: 0.493

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 896/2178=41.1% -

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;