9-122628962-G-A

Variant names:

• chr9-122628962-G-A
• rs1476860
• NM_001004450.3:c.571C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001004450.3(OR1B1):​c.571C>T​(p.Arg191*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,613,450 control chromosomes in the GnomAD database, including 83,449 homozygotes. 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: 𝑓 0.26 (6514 hom., cov: 31)
  • Exomes 𝑓: 0.31 (76935 hom.)
• Consequence: OR1B1 NM_001004450.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170
• Publications: 36 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1B1	NM_001004450.3	MANE Select	c.571C>T	p.Arg191*	stop_gained	Exon 2 of 2	NP_001004450.2
	OR1B1	NM_001409693.1		c.571C>T	p.Arg191*	stop_gained	Exon 2 of 2	NP_001396622.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1B1	ENST00000623530.2	TSL:6 MANE Select	c.571C>T	p.Arg191*	stop_gained	Exon 2 of 2	ENSP00000485577.2
	OR1B1	ENST00000707075.1		c.571C>T	p.Arg191*	stop_gained	Exon 2 of 2	ENSP00000516726.1
	ENSG00000234156	ENST00000419604.1	TSL:5	n.279-8144G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39796 AN: 151892 Hom.: 6505 Cov.: 31

Gnomad AFR AF: 0.0940

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.287

GnomAD2 exomes AF: 0.355 AC: 88789 AN: 250020 AF XY: 0.354

Gnomad AFR exome AF: 0.0840

Gnomad AMR exome AF: 0.542

Gnomad ASJ exome AF: 0.347

Gnomad EAS exome AF: 0.611

Gnomad FIN exome AF: 0.275

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.312 AC: 456352 AN: 1461440 Hom.: 76935 Cov.: 51 AF XY: 0.316 AC XY: 229406 AN XY: 726994

African (AFR) AF: 0.0805 AC: 2693 AN: 33472

American (AMR) AF: 0.529 AC: 23626 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 9140 AN: 26130

East Asian (EAS) AF: 0.599 AC: 23766 AN: 39680

South Asian (SAS) AF: 0.458 AC: 39532 AN: 86238

European-Finnish (FIN) AF: 0.281 AC: 15004 AN: 53400

Middle Eastern (MID) AF: 0.281 AC: 1623 AN: 5768

European-Non Finnish (NFE) AF: 0.290 AC: 322301 AN: 1111702

Other (OTH) AF: 0.309 AC: 18667 AN: 60380

GnomAD4 genome AF: 0.262 AC: 39820 AN: 152010 Hom.: 6514 Cov.: 31 AF XY: 0.270 AC XY: 20086 AN XY: 74302

African (AFR) AF: 0.0940 AC: 3899 AN: 41488

American (AMR) AF: 0.426 AC: 6499 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3468

East Asian (EAS) AF: 0.593 AC: 3049 AN: 5142

South Asian (SAS) AF: 0.460 AC: 2218 AN: 4818

European-Finnish (FIN) AF: 0.267 AC: 2822 AN: 10560

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19321 AN: 67968

Other (OTH) AF: 0.286 AC: 601 AN: 2104

Alfa AF: 0.289 Hom.: 34419

Bravo AF: 0.264

TwinsUK AF: 0.294 AC: 1090

ALSPAC AF: 0.301 AC: 1160

ESP6500AA AF: 0.0903 AC: 398

ESP6500EA AF: 0.297 AC: 2554

ExAC AF: 0.340 AC: 41248

Asia WGS AF: 0.481 AC: 1672 AN: 3478

EpiCase AF: 0.288

EpiControl AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	34
DANN	Benign	0.93
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.043	N
PhyloP100		-0.17
GERP RS		-6.0
Mutation Taster		=198/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: 2

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

Other links and lift over

dbSNP: rs1476860; hg19: chr9-125391241; COSMIC: COSV59171571;