9-122750491-T-C

Position:

• chr9-122750491-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.5023984E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR1L6	NM_001004453.3	c.644T>C	p.Ile215Thr	missense_variant	2/2	ENST00000304720.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR1L6	ENST00000304720.3	c.644T>C	p.Ile215Thr	missense_variant	2/2		NM_001004453.3	P1
OR1L6	ENST00000373684.1	c.752T>C	p.Ile251Thr	missense_variant	1/1

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

GnomAD3 exomes AF: 0.899 AC: 171260 AN: 190408 Hom.: 83693 AF XY: 0.902 AC XY: 91463 AN XY: 101368

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 SAS exome AF: 0.904

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

Gnomad4 AFR exome AF: 0.651

Gnomad4 AMR exome AF: 0.968

Gnomad4 ASJ exome AF: 0.941

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.932

Gnomad4 FIN exome AF: 0.905

Gnomad4 NFE exome AF: 0.925

Gnomad4 OTH exome AF: 0.916

GnomAD4 genome AF: 0.894 AC: 117093 AN: 130924 Hom.: 53140 Cov.: 16 AF XY: 0.892 AC XY: 55586 AN XY: 62306

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.946

Gnomad4 ASJ AF: 0.955

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.962

Gnomad4 OTH AF: 0.925

Alfa AF: 0.919 Hom.: 12590

Bravo AF: 0.899

ExAC AF: 0.876 AC: 104783

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.68	T;T
MetaRNN	Benign	9.5e-7	T;T
MetaSVM	Benign	-0.89	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.96	.;D
Vest4		0.29
MPC		0.40
ClinPred		0.069	T
GERP RS		3.4
Varity_R		0.34
gMVP		0.17

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

LitVar

Other links and lift over

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