rs11755177

Positions:

• chr6-29440198-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_013941.4(OR10C1):​c.183C>T​(p.Phe61Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,613,834 control chromosomes in the GnomAD database, including 646 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 0.039 (275 hom., cov: 32)
  • Exomes 𝑓: 0.011 (371 hom.)
• Consequence: OR10C1 NM_013941.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.516 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR10C1	NM_013941.4	c.183C>T	p.Phe61Phe	synonymous_variant	1/1	ENST00000444197.3	NP_039229.3
OR11A1	NM_001394828.1	c.-388-8211G>A		intron_variant		ENST00000377149.5	NP_001381757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR10C1	ENST00000444197.3	c.183C>T	p.Phe61Phe	synonymous_variant	1/1	6	NM_013941.4	ENSP00000419119.1
OR11A1	ENST00000377149.5	c.-388-8211G>A		intron_variant		6	NM_001394828.1	ENSP00000366354.1
OR10C1	ENST00000622521.1	c.189C>T	p.Phe63Phe	synonymous_variant	1/1	6		ENSP00000481429.1

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5932 AN: 152160 Hom.: 275 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: 4379 AN: 247050 Hom.: 126 AF XY: 0.0157 AC XY: 2117 AN XY: 134482

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0206

Gnomad EAS exome AF: 0.00875

Gnomad SAS exome AF: 0.0142

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.00879

Gnomad OTH exome AF: 0.0171

GnomAD4 exome AF: 0.0113 AC: 16575 AN: 1461556 Hom.: 371 Cov.: 35 AF XY: 0.0111 AC XY: 8043 AN XY: 727090

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: 0.000602

Gnomad4 NFE exome AF: 0.00748

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0390 AC: 5943 AN: 152278 Hom.: 275 Cov.: 32 AF XY: 0.0374 AC XY: 2787 AN XY: 74460

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: 0.0431

Alfa AF: 0.0182 Hom.: 128

Bravo AF: 0.0448

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
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.8
DANN	Benign	0.61

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: rs11755177; hg19: chr6-29407975;