rs2074466

Positions:

• chr6-29440536-C-A
• chr6-29440536-C-G

Variant summary

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

The NM_013941.4(OR10C1):​c.521C>A​(p.Pro174Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,613,412 control chromosomes in the GnomAD database, including 19,193 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.13 (1428 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17765 hom.)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939

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=0.0065612793).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.521C>A	p.Pro174Gln	missense_variant	1/1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8549G>T		intron_variant		ENST00000377149.5	NP_001381757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10C1	ENST00000444197.3	c.521C>A	p.Pro174Gln	missense_variant	1/1	6	NM_013941.4	ENSP00000419119.1
OR11A1	ENST00000377149.5	c.-388-8549G>T		intron_variant		6	NM_001394828.1	ENSP00000366354.1
OR10C1	ENST00000622521.1	c.527C>A	p.Pro176Gln	missense_variant	1/1	6		ENSP00000481429.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19390 AN: 152048 Hom.: 1423 Cov.: 32

Gnomad AFR AF: 0.0488

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.134

GnomAD3 exomes AF: 0.165 AC: 40579 AN: 246616 Hom.: 3813 AF XY: 0.161 AC XY: 21683 AN XY: 134280

Gnomad AFR exome AF: 0.0466

Gnomad AMR exome AF: 0.261

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.225

Gnomad SAS exome AF: 0.144

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.151 AC: 221206 AN: 1461246 Hom.: 17765 Cov.: 35 AF XY: 0.152 AC XY: 110280 AN XY: 726966

Gnomad4 AFR exome AF: 0.0438

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.137

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.127 AC: 19398 AN: 152166 Hom.: 1428 Cov.: 32 AF XY: 0.130 AC XY: 9669 AN XY: 74378

Gnomad4 AFR AF: 0.0485

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.133

Alfa AF: 0.140 Hom.: 1457

Bravo AF: 0.131

TwinsUK AF: 0.147 AC: 546

ALSPAC AF: 0.155 AC: 599

ESP6500AA AF: 0.0493 AC: 149

ESP6500EA AF: 0.148 AC: 802

ExAC AF: 0.157 AC: 18708

Asia WGS AF: 0.142 AC: 495 AN: 3478

EpiCase AF: 0.149

EpiControl AF: 0.157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.75
DANN	Benign	0.67
DEOGEN2	Benign	0.00040	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0020	N
MetaRNN	Benign	0.0066	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.37	N;.
PrimateAI	Benign	0.19	T
PROVEAN	Benign	1.8	N;.
REVEL	Benign	0.020
Sift	Benign	0.12	T;.
Polyphen		0.027	B;.
MPC		0.33
ClinPred		0.00047	T
GERP RS		-0.47
Varity_R		0.051
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs2074466; hg19: chr6-29408313; COSMIC: COSV65823032;