11-124570721-C-T

Variant names:

• chr11-124570721-C-T
• rs12792184
• NM_001005194.2:c.602C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005194.2(OR8A1):​c.602C>T​(p.Ser201Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 1,613,782 control chromosomes in the GnomAD database, including 463,759 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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: 𝑓 0.76 (44034 hom., cov: 31)
  • Exomes 𝑓: 0.76 (419725 hom.)
• Consequence: OR8A1 NM_001005194.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.811
• Publications: 25 publications found

Genes affected

OR8A1 (HGNC:8469): (olfactory receptor family 8 subfamily A member 1) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.057802E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005194.2. 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
	OR8A1	NM_001005194.2	MANE Select	c.602C>T	p.Ser201Leu	missense	Exon 1 of 1	NP_001005194.2	A0A286YEW5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR8A1	ENST00000284287.6	TSL:6 MANE Select	c.602C>T	p.Ser201Leu	missense	Exon 1 of 1	ENSP00000284287.4	A0A286YEW5
	OR8A1	ENST00000642111.1		c.653C>T	p.Ser218Leu	missense	Exon 1 of 1	ENSP00000492999.1	Q8NGG7
	OR8A1	ENST00000641670.1		c.602C>T	p.Ser201Leu	missense	Exon 2 of 2	ENSP00000492950.1	A0A286YEW5

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115447 AN: 151930 Hom.: 44005 Cov.: 31

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.779

GnomAD2 exomes AF: 0.764 AC: 191609 AN: 250816 AF XY: 0.764

Gnomad AFR exome AF: 0.753

Gnomad AMR exome AF: 0.766

Gnomad ASJ exome AF: 0.757

Gnomad EAS exome AF: 0.896

Gnomad FIN exome AF: 0.771

Gnomad NFE exome AF: 0.745

Gnomad OTH exome AF: 0.767

GnomAD4 exome AF: 0.757 AC: 1106665 AN: 1461734 Hom.: 419725 Cov.: 55 AF XY: 0.757 AC XY: 550450 AN XY: 727190

African (AFR) AF: 0.758 AC: 25357 AN: 33472

American (AMR) AF: 0.770 AC: 34406 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 19831 AN: 26134

East Asian (EAS) AF: 0.918 AC: 36446 AN: 39698

South Asian (SAS) AF: 0.755 AC: 65127 AN: 86258

European-Finnish (FIN) AF: 0.771 AC: 41180 AN: 53418

Middle Eastern (MID) AF: 0.757 AC: 4366 AN: 5768

European-Non Finnish (NFE) AF: 0.750 AC: 833643 AN: 1111894

Other (OTH) AF: 0.767 AC: 46309 AN: 60392

GnomAD4 genome AF: 0.760 AC: 115524 AN: 152048 Hom.: 44034 Cov.: 31 AF XY: 0.763 AC XY: 56727 AN XY: 74320

African (AFR) AF: 0.757 AC: 31372 AN: 41462

American (AMR) AF: 0.787 AC: 12026 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2591 AN: 3468

East Asian (EAS) AF: 0.899 AC: 4647 AN: 5170

South Asian (SAS) AF: 0.753 AC: 3620 AN: 4808

European-Finnish (FIN) AF: 0.767 AC: 8113 AN: 10584

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50778 AN: 67960

Other (OTH) AF: 0.781 AC: 1647 AN: 2108

Alfa AF: 0.756 Hom.: 168424

Bravo AF: 0.762

TwinsUK AF: 0.746 AC: 2766

ALSPAC AF: 0.758 AC: 2921

ESP6500AA AF: 0.760 AC: 3347

ESP6500EA AF: 0.746 AC: 6412

ExAC AF: 0.760 AC: 92308

Asia WGS AF: 0.829 AC: 2885 AN: 3478

EpiCase AF: 0.758

EpiControl AF: 0.752

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.8
DANN	Benign	0.078
DEOGEN2	Benign	0.0088	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.00066	N
LIST_S2	Benign	0.016	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.61	N
PhyloP100		0.81
PrimateAI	Benign	0.22	T
REVEL	Benign	0.10
Polyphen		0.0	B
MPC		0.057
ClinPred		0.0067	T
GERP RS		5.0
Varity_R		0.047
gMVP		0.27
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12792184; hg19: chr11-124440617; COSMIC: COSV52508089; COSMIC: COSV52508089;