rs9804659

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-55554735-A-C
• chr11-55554735-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001920.3(OR4C15):​c.267A>C​(p.Lys89Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: OR4C15 NM_001001920.3 missense
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15633643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4C15	NM_001001920.3	c.267A>C	p.Lys89Asn	missense_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>C	p.Lys89Asn	missense_variant	Exon 1 of 1		NM_001001920.3	ENSP00000493126.1
OR4C15	ENST00000314644.2	c.429A>C	p.Lys143Asn	missense_variant	Exon 1 of 1	6		ENSP00000324958.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461684 Hom.: 0 Cov.: 38 AF XY: 0.00000275 AC XY: 2 AN XY: 727154

African (AFR) AF: 0.0000598 AC: 2 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111928

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Uncertain	1.0
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	.;L
PhyloP100		-1.1
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.4	D;.
REVEL	Benign	0.072
Sift	Benign	0.070	T;.
Sift4G	Benign	0.11	T;.
Polyphen		0.18	.;B
Vest4		0.51
MutPred		0.57		.;Loss of methylation at K89 (P = 0.0149);
MVP		0.13
ClinPred		0.22	T
GERP RS		2.8
PromoterAI		0.020	Neutral
Varity_R		0.068
gMVP		0.058
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;