9-122750491-T-C

Variant names:

• chr9-122750491-T-C
• rs10985760
• NM_001004453.3:c.644T>C
• OR1L6 p.Ile215Thr

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001004453.3(OR1L6):​c.644T>C​(p.Ile215Thr) variant causes a missense change. 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 0.89 (53140 hom., cov: 16)
  • Exomes 𝑓: 0.92 (373455 hom.)
• Consequence: OR1L6 NM_001004453.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83
• Publications: 18 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.5023984E-7).
• BS2: High Homozygotes in GnomAd4 at 53140 AR gene

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.644T>C	p.Ile215Thr	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.644T>C	p.Ile215Thr	missense	Exon 2 of 2	ENSP00000304235.2	A0A0C4DFP2
	OR1L6	ENST00000373684.1	TSL:6	c.752T>C	p.Ile251Thr	missense	Exon 1 of 1	ENSP00000362788.1	Q8NGR2

Frequencies

GnomAD3 genomes AF: 0.895 AC: 117061 AN: 130832 Hom.: 53138 Cov.: 16

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.952

Gnomad NFE AF: 0.962

Gnomad OTH AF: 0.926

GnomAD2 exomes AF: 0.899 AC: 171260 AN: 190408 AF XY: 0.902

Gnomad AFR exome AF: 0.611

Gnomad AMR exome AF: 0.962

Gnomad ASJ exome AF: 0.901

Gnomad EAS exome AF: 0.998

Gnomad FIN exome AF: 0.809

Gnomad NFE exome AF: 0.919

Gnomad OTH exome AF: 0.913

GnomAD4 exome AF: 0.922 AC: 767176 AN: 832052 Hom.: 373455 Cov.: 12 AF XY: 0.925 AC XY: 400011 AN XY: 432604

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

African (AFR) AF: 0.651 AC: 14537 AN: 22324

American (AMR) AF: 0.968 AC: 39748 AN: 41068

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 18550 AN: 19722

East Asian (EAS) AF: 0.999 AC: 36648 AN: 36670

South Asian (SAS) AF: 0.932 AC: 61752 AN: 66284

European-Finnish (FIN) AF: 0.905 AC: 43336 AN: 47910

Middle Eastern (MID) AF: 0.880 AC: 2725 AN: 3098

European-Non Finnish (NFE) AF: 0.925 AC: 513732 AN: 555506

Other (OTH) AF: 0.916 AC: 36148 AN: 39470

⚠️ 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: 0.894 AC: 117093 AN: 130924 Hom.: 53140 Cov.: 16 AF XY: 0.892 AC XY: 55586 AN XY: 62306

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

African (AFR) AF: 0.734 AC: 25714 AN: 35040

American (AMR) AF: 0.946 AC: 11751 AN: 12424

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 3032 AN: 3174

East Asian (EAS) AF: 0.999 AC: 4408 AN: 4414

South Asian (SAS) AF: 0.943 AC: 3201 AN: 3396

European-Finnish (FIN) AF: 0.893 AC: 7666 AN: 8580

Middle Eastern (MID) AF: 0.956 AC: 260 AN: 272

European-Non Finnish (NFE) AF: 0.962 AC: 58783 AN: 61134

Other (OTH) AF: 0.925 AC: 1562 AN: 1688

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.876 Hom.: 17110

Bravo AF: 0.899

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.68	T
MetaRNN	Benign	9.5e-7	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.8
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.13
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.010	D
Varity_R		0.34
gMVP		0.17
Mutation Taster		=71/29	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10985760; hg19: chr9-125512770; COSMIC: COSV59027771;