chr11-55554735-A-G

Position:

• chr11-55554735-A-G

Variant summary

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

The NM_001001920.3(OR4C15):​c.267A>G​(p.Lys89Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,613,484 control chromosomes in the GnomAD database, including 57,883 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 0.24 (4924 hom., cov: 32)
  • Exomes 𝑓: 0.26 (52959 hom.)
• Consequence: OR4C15 NM_001001920.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

OR4C15 (HGNC:15171): (olfactory receptor family 4 subfamily C member 15) 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=-0.88).
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4C15	NM_001001920.3	c.267A>G	p.Lys89Lys	synonymous_variant	1/1	ENST00000642128.1	NP_001001920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4C15	ENST00000642128.1	c.267A>G	p.Lys89Lys	synonymous_variant	1/1		NM_001001920.3	ENSP00000493126.1
OR4C15	ENST00000314644.2	c.429A>G	p.Lys143Lys	synonymous_variant	1/1	6		ENSP00000324958.2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36137 AN: 151836 Hom.: 4908 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.264

GnomAD3 exomes AF: 0.287 AC: 72053 AN: 250888 Hom.: 11168 AF XY: 0.284 AC XY: 38457 AN XY: 135574

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.409

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.384

Gnomad SAS exome AF: 0.244

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.300

GnomAD4 exome AF: 0.265 AC: 386666 AN: 1461530 Hom.: 52959 Cov.: 38 AF XY: 0.265 AC XY: 192686 AN XY: 727068

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.238 AC: 36168 AN: 151954 Hom.: 4924 Cov.: 32 AF XY: 0.241 AC XY: 17935 AN XY: 74278

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.273

Alfa AF: 0.248 Hom.: 2710

Bravo AF: 0.239

Asia WGS AF: 0.300 AC: 1042 AN: 3478

EpiCase AF: 0.280

EpiControl AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9804659; hg19: chr11-55322211; COSMIC: COSV58953461;