6-29440193-T-C

Variant names:

• chr6-29440193-T-C
• rs2074469
• NM_013941.4:c.178T>C

Variant summary

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

The NM_013941.4(OR10C1):​c.178T>C​(p.Phe60Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,613,666 control chromosomes in the GnomAD database, including 28,981 homozygotes. 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 0.16 (2223 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26758 hom.)
• Consequence: OR10C1 NM_013941.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.767
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037362874).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.178T>C	p.Phe60Leu	missense_variant	Exon 1 of 1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8206A>G		intron_variant	Intron 1 of 4	ENST00000377149.5	NP_001381757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR10C1	ENST00000444197.3	c.178T>C	p.Phe60Leu	missense_variant	Exon 1 of 1	6	NM_013941.4	ENSP00000419119.1
OR11A1	ENST00000377149.5	c.-388-8206A>G		intron_variant	Intron 1 of 4	6	NM_001394828.1	ENSP00000366354.1
OR10C1	ENST00000622521.1	c.184T>C	p.Phe62Leu	missense_variant	Exon 1 of 1	6		ENSP00000481429.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24821 AN: 152020 Hom.: 2218 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.167

GnomAD2 exomes AF: 0.194 AC: 47950 AN: 247058 AF XY: 0.191

Gnomad AFR exome AF: 0.0846

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.226

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.188 AC: 275484 AN: 1461528 Hom.: 26758 Cov.: 35 AF XY: 0.188 AC XY: 136794 AN XY: 727076

African (AFR) AF: 0.0820 AC: 2745 AN: 33480

American (AMR) AF: 0.271 AC: 12138 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 4494 AN: 26136

East Asian (EAS) AF: 0.220 AC: 8716 AN: 39700

South Asian (SAS) AF: 0.163 AC: 14021 AN: 86256

European-Finnish (FIN) AF: 0.168 AC: 8931 AN: 53082

Middle Eastern (MID) AF: 0.160 AC: 920 AN: 5768

European-Non Finnish (NFE) AF: 0.191 AC: 212766 AN: 1111992

Other (OTH) AF: 0.178 AC: 10753 AN: 60390

GnomAD4 genome AF: 0.163 AC: 24831 AN: 152138 Hom.: 2223 Cov.: 32 AF XY: 0.164 AC XY: 12216 AN XY: 74380

African (AFR) AF: 0.0876 AC: 3639 AN: 41546

American (AMR) AF: 0.210 AC: 3212 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3468

East Asian (EAS) AF: 0.235 AC: 1215 AN: 5160

South Asian (SAS) AF: 0.157 AC: 756 AN: 4826

European-Finnish (FIN) AF: 0.170 AC: 1802 AN: 10576

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.193 AC: 13090 AN: 67962

Other (OTH) AF: 0.166 AC: 349 AN: 2108

Alfa AF: 0.184 Hom.: 10739

Bravo AF: 0.167

TwinsUK AF: 0.187 AC: 693

ALSPAC AF: 0.194 AC: 748

ESP6500AA AF: 0.0834 AC: 252

ESP6500EA AF: 0.188 AC: 1017

ExAC AF: 0.187 AC: 22355

Asia WGS AF: 0.156 AC: 542 AN: 3478

EpiCase AF: 0.188

EpiControl AF: 0.198

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;.
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.085
FATHMM_MKL	Benign	0.47	N
MetaRNN	Benign	0.0037	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.8	L;.
PhyloP100		0.77
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.3	D;.
REVEL	Benign	0.13
Sift	Benign	0.068	T;.
Polyphen		1.0	D;.
MutPred		0.47		Loss of methylation at R63 (P = 0.1183);.;
MPC		1.2
ClinPred		0.022	T
GERP RS		3.6
PromoterAI		-0.0096	Neutral
Varity_R		0.54
gMVP		0.24
Mutation Taster		=89/11	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2074469; hg19: chr6-29407970; COSMIC: COSV65822234;