rs200264223

Variant names:

• chr9-122675799-G-A
• rs200264223
• NM_001005234.1:c.670G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-122675799-G-A
• chr9-122675799-G-C
• chr9-122675799-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001005234.1(OR1L3):​c.670G>A​(p.Ala224Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000239 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: OR1L3 NM_001005234.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.401
• Publications: 2 publications found

Genes affected

OR1L3 (HGNC:8215): (olfactory receptor family 1 subfamily L member 3) 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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052253485).
• BP6: Variant 9-122675799-G-A is Benign according to our data. Variant chr9-122675799-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2600495.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005234.1. 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
	OR1L3	NM_001005234.1	MANE Select	c.670G>A	p.Ala224Thr	missense	Exon 1 of 1	NP_001005234.1	A0A126GVD1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1L3	ENST00000304820.5	TSL:6 MANE Select	c.670G>A	p.Ala224Thr	missense	Exon 1 of 1	ENSP00000302863.2	Q8NH93

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251116 AF XY: 0.0000590

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000239 AC: 35 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20 AN XY: 727230

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1112000

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.4
DANN	Benign	0.60
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.027	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.40
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.030
Sift	Benign	0.49	T
Sift4G	Benign	0.71	T
Polyphen		0.032	B
Vest4		0.032
MutPred		0.44		Loss of ubiquitination at K227 (P = 0.1179)
MVP		0.13
MPC		0.029
ClinPred		0.019	T
GERP RS		-0.90
Varity_R		0.034
gMVP		0.043
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs200264223; hg19: chr9-125438078; COSMIC: COSV59170367;