chr11-55554677-C-A

Variant names:

• chr11-55554677-C-A
• rs375390291
• NM_001001920.3:c.209C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001001920.3(OR4C15):​c.209C>A​(p.Ala70Glu) 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 1,461,120 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A70V) has been classified as Uncertain significance.

• 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: 0.787
• Publications: 3 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37467813).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001920.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4C15	NM_001001920.3	MANE Select	c.209C>A	p.Ala70Glu	missense	Exon 1 of 1	NP_001001920.2	Q8NGM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4C15	ENST00000642128.1	MANE Select	c.209C>A	p.Ala70Glu	missense	Exon 1 of 1	ENSP00000493126.1	Q8NGM1
	OR4C15	ENST00000314644.2	TSL:6	c.371C>A	p.Ala124Glu	missense	Exon 1 of 1	ENSP00000324958.2	A0A2C9F2M4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250678 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461120 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726914

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

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

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111932

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.97
Eigen	Benign	0.011
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.79
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.011	D
Polyphen		0.98	D
Vest4		0.53
MutPred		0.51		Loss of catalytic residue at C71 (P = 0.0507)
MVP		0.40
ClinPred		0.85	D
GERP RS		3.2
PromoterAI		-0.0092	Neutral
Varity_R		0.46
gMVP		0.22
Mutation Taster		=99/1	polymorphism

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: rs375390291; hg19: chr11-55322153;