rs17184009

Positions:

• chr6-29440178-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_013941.4(OR10C1):​c.163C>T​(p.Gln55Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00871 in 1,613,722 control chromosomes in the GnomAD database, including 274 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.025 (115 hom., cov: 32)
  • Exomes 𝑓: 0.0070 (159 hom.)
• Consequence: OR10C1 NM_013941.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.70

Genes affected

OR10C1 (HGNC:8165): (olfactory receptor family 10 subfamily C 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

OR11A1 (HGNC:8176): (olfactory receptor family 11 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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10C1	NM_013941.4	c.163C>T	p.Gln55Ter	stop_gained	1/1	ENST00000444197.3
OR11A1	NM_001394828.1	c.-388-8191G>A		intron_variant		ENST00000377149.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10C1	ENST00000444197.3	c.163C>T	p.Gln55Ter	stop_gained	1/1		NM_013941.4	P1
OR11A1	ENST00000377149.5	c.-388-8191G>A		intron_variant			NM_001394828.1	P1
OR10C1	ENST00000622521.1	c.169C>T	p.Gln57Ter	stop_gained	1/1

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3852 AN: 152150 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0744

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00551

Gnomad OTH AF: 0.0330

GnomAD3 exomes AF: 0.0109 AC: 2704 AN: 247104 Hom.: 56 AF XY: 0.00931 AC XY: 1253 AN XY: 134522

Gnomad AFR exome AF: 0.0804

Gnomad AMR exome AF: 0.0140

Gnomad ASJ exome AF: 0.0206

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00165

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.00591

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.00697 AC: 10193 AN: 1461454 Hom.: 159 Cov.: 31 AF XY: 0.00667 AC XY: 4849 AN XY: 727042

Gnomad4 AFR exome AF: 0.0798

Gnomad4 AMR exome AF: 0.0154

Gnomad4 ASJ exome AF: 0.0213

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00174

Gnomad4 FIN exome AF: 0.000434

Gnomad4 NFE exome AF: 0.00466

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0254 AC: 3861 AN: 152268 Hom.: 115 Cov.: 32 AF XY: 0.0240 AC XY: 1785 AN XY: 74454

Gnomad4 AFR AF: 0.0744

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00551

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.00997 Hom.: 35

Bravo AF: 0.0293

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.0778 AC: 235

ESP6500EA AF: 0.00720 AC: 39

ExAC AF: 0.0113 AC: 1355

Asia WGS AF: 0.00751 AC: 26 AN: 3478

EpiCase AF: 0.00687

EpiControl AF: 0.00723

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.84	D
MutationTaster	Benign	6.6e-20	P;P;P
GERP RS		3.7

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: rs17184009; hg19: chr6-29407955; COSMIC: COSV105318044;