11-55554735-A-G

Variant names:

• chr11-55554735-A-G
• rs9804659
• NM_001001920.3:c.267A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OR4C15	NM_001001920.3	c.267A>G	p.Lys89Lys	synonymous_variant	Exon 1 of 1	ENST00000642128.1	NP_001001920.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4C15	ENST00000642128.1	c.267A>G	p.Lys89Lys	synonymous_variant	Exon 1 of 1		NM_001001920.3	ENSP00000493126.1
OR4C15	ENST00000314644.2	c.429A>G	p.Lys143Lys	synonymous_variant	Exon 1 of 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

GnomAD2 exomes AF: 0.287 AC: 72053 AN: 250888 AF XY: 0.284

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 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

African (AFR) AF: 0.116 AC: 3887 AN: 33468

American (AMR) AF: 0.399 AC: 17811 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 6522 AN: 26126

East Asian (EAS) AF: 0.357 AC: 14178 AN: 39692

South Asian (SAS) AF: 0.246 AC: 21240 AN: 86252

European-Finnish (FIN) AF: 0.313 AC: 16690 AN: 53332

Middle Eastern (MID) AF: 0.347 AC: 2000 AN: 5766

European-Non Finnish (NFE) AF: 0.259 AC: 288288 AN: 1111822

Other (OTH) AF: 0.266 AC: 16050 AN: 60390

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

African (AFR) AF: 0.123 AC: 5117 AN: 41502

American (AMR) AF: 0.331 AC: 5043 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3470

East Asian (EAS) AF: 0.363 AC: 1861 AN: 5128

South Asian (SAS) AF: 0.248 AC: 1197 AN: 4820

European-Finnish (FIN) AF: 0.322 AC: 3401 AN: 10558

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17781 AN: 67928

Other (OTH) AF: 0.273 AC: 574 AN: 2104

Alfa AF: 0.247 Hom.: 2720

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
PhyloP100		-1.1
PromoterAI		-0.0058	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9804659; hg19: chr11-55322211; COSMIC: COSV58953461;