9-122750265-C-T

Variant names:

• chr9-122750265-C-T
• rs377073162
• NM_001004453.3:c.418C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004453.3(OR1L6):​c.418C>T​(p.Arg140Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,613,824 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: OR1L6 NM_001004453.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.57
• Publications: 1 publications found

Genes affected

OR1L6 (HGNC:8218): (olfactory receptor family 1 subfamily L member 6) 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0153669715).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004453.3. 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
	OR1L6	NM_001004453.3	MANE Select	c.418C>T	p.Arg140Trp	missense	Exon 2 of 2	NP_001004453.2	A0A0C4DFP2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR1L6	ENST00000304720.3	TSL:6 MANE Select	c.418C>T	p.Arg140Trp	missense	Exon 2 of 2	ENSP00000304235.2	A0A0C4DFP2
	OR1L6	ENST00000373684.1	TSL:6	c.526C>T	p.Arg176Trp	missense	Exon 1 of 1	ENSP00000362788.1	Q8NGR2

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152088 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000203 AC: 51 AN: 251394 AF XY: 0.000287

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000233 AC: 340 AN: 1461618 Hom.: 1 Cov.: 81 AF XY: 0.000283 AC XY: 206 AN XY: 727114

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000896 AC: 3 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44718

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

East Asian (EAS) AF: 0.00118 AC: 47 AN: 39688

South Asian (SAS) AF: 0.00145 AC: 125 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.000133 AC: 148 AN: 1111832

Other (OTH) AF: 0.000199 AC: 12 AN: 60380

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152206 Hom.: 0 Cov.: 31 AF XY: 0.000161 AC XY: 12 AN XY: 74424

African (AFR) AF: 0.0000482 AC: 2 AN: 41518

American (AMR) AF: 0.000196 AC: 3 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000125

ExAC AF: 0.000354 AC: 43

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.085
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.4
DANN	Benign	0.92
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.0012	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-3.6
PrimateAI	Benign	0.17	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.065
Sift	Benign	0.036	D
Sift4G	Uncertain	0.045	D
Polyphen		0.081	B
Vest4		0.17
MVP		0.24
MPC		0.31
ClinPred		0.060	T
GERP RS		-3.0
Varity_R		0.13
gMVP		0.26
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs377073162; hg19: chr9-125512544; COSMIC: COSV59028829;