9-122567981-C-A

Variant names:

• chr9-122567981-C-A
• NM_001004454.2:c.497G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004454.2(OR1L8):​c.497G>T​(p.Arg166Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OR1L8 NM_001004454.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14

Genes affected

OR1L8 (HGNC:15110): (olfactory receptor family 1 subfamily L member 8) 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]

ENSG00000234156 (HGNC:):

OR1J2 (HGNC:8209): (olfactory receptor family 1 subfamily J member 2) 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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14098763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR1L8	NM_001004454.2	c.497G>T	p.Arg166Leu	missense_variant	Exon 5 of 5	ENST00000641027.1	NP_001004454.1
OR1L8	XM_017014285.2	c.497G>T	p.Arg166Leu	missense_variant	Exon 3 of 4		XP_016869774.1
OR1L8	XM_017014286.2	c.497G>T	p.Arg166Leu	missense_variant	Exon 2 of 2		XP_016869775.1
OR1J2	XR_007061271.1	n.1541-11972C>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR1L8	ENST00000641027.1	c.497G>T	p.Arg166Leu	missense_variant	Exon 5 of 5		NM_001004454.2	ENSP00000493411.1
ENSG00000234156	ENST00000431442.2	n.1363-38665C>A		intron_variant	Intron 7 of 9	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0050
DANN	Benign	0.96
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.56	.;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Benign	0.17	T
PROVEAN	Pathogenic	-4.5	.;D
REVEL	Benign	0.092
Sift	Benign	0.047	.;D
Sift4G	Uncertain	0.045	.;D
Polyphen		0.0070	B;B
Vest4		0.094
MutPred		0.58		Loss of catalytic residue at R166 (P = 0.0241);Loss of catalytic residue at R166 (P = 0.0241);
MVP		0.12
MPC		0.092
ClinPred		0.63	D
GERP RS		-9.0
Varity_R		0.13
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-125330260; COSMIC: COSV100508549;