rs11755182

chr6-29440280-C-Achr6-29440280-C-T

Variant summary

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

The NM_013941.4(OR10C1):c.265C>A(p.Arg89Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,934 control chromosomes in the GnomAD database, including 647 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.039 (276 hom., cov: 32)
  • Exomes 𝑓: 0.011 (371 hom.)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036697984).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR10C1	NM_013941.4	c.265C>A	p.Arg89Ser	missense_variant	1/1	ENST00000444197.3
OR11A1	NM_001394828.1	c.-388-8293G>T		intron_variant		ENST00000377149.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR10C1	ENST00000444197.3	c.265C>A	p.Arg89Ser	missense_variant	1/1		NM_013941.4	P1
OR11A1	ENST00000377149.5	c.-388-8293G>T		intron_variant			NM_001394828.1	P1
OR10C1	ENST00000622521.1	c.271C>A	p.Arg91Ser	missense_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5935 AN: 152132 Hom.: 276 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0237

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00844

Gnomad OTH AF: 0.0435

GnomAD3 exomes AF: 0.0177 AC: 4373 AN: 247210 Hom.: 126 AF XY: 0.0157 AC XY: 2112 AN XY: 134536

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0193

Gnomad ASJ exome AF: 0.0206

Gnomad EAS exome AF: 0.00880

Gnomad SAS exome AF: 0.0142

Gnomad FIN exome AF: 0.000694

Gnomad NFE exome AF: 0.00878

Gnomad OTH exome AF: 0.0171

GnomAD4 exome AF: 0.0113 AC: 16573 AN: 1461682 Hom.: 371 Cov.: 35 AF XY: 0.0111 AC XY: 8041 AN XY: 727140

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.0211

Gnomad4 ASJ exome AF: 0.0214

Gnomad4 EAS exome AF: 0.00398

Gnomad4 SAS exome AF: 0.0134

Gnomad4 FIN exome AF: 0.000620

Gnomad4 NFE exome AF: 0.00748

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0391 AC: 5946 AN: 152252 Hom.: 276 Cov.: 32 AF XY: 0.0374 AC XY: 2788 AN XY: 74452

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0235

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00844

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0124 Hom.: 42

Bravo AF: 0.0448

TwinsUK AF: 0.0108 AC: 40

ALSPAC AF: 0.00856 AC: 33

ESP6500AA AF: 0.118 AC: 357

ESP6500EA AF: 0.00868 AC: 47

ExAC AF: 0.0185 AC: 2230

Asia WGS AF: 0.0240 AC: 82 AN: 3478

EpiCase AF: 0.00971

EpiControl AF: 0.0106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.52
Cadd	Benign	9.5
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0068	T;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.11	N
MetaRNN	Benign	0.0037	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.61	N;.
MutationTaster	Benign	0.66	P;P;P
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-3.1	D;.
REVEL	Benign	0.060
Sift	Uncertain	0.011	D;.
Polyphen		0.69	P;.
MPC		0.39
ClinPred		0.011	T
GERP RS		2.4
Varity_R		0.24
gMVP		0.29

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: rs11755182; hg19: chr6-29408057;