11-55554677-C-G

Variant names:

• chr11-55554677-C-G
• rs375390291
• NM_001001920.3:c.209C>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.209C>G​(p.Ala70Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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)
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18588915).

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>G	p.Ala70Gly	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>G	p.Ala70Gly	missense	Exon 1 of 1	ENSP00000493126.1	Q8NGM1
	OR4C15	ENST00000314644.2	TSL:6	c.371C>G	p.Ala124Gly	missense	Exon 1 of 1	ENSP00000324958.2	A0A2C9F2M4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.96
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.79
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.048
Sift	Benign	0.13	T
Sift4G	Benign	0.12	T
Polyphen		0.10	B
Vest4		0.32
MutPred		0.42		Loss of catalytic residue at A70 (P = 0.0528)
MVP		0.20
ClinPred		0.29	T
GERP RS		3.2
PromoterAI		-0.019	Neutral
Varity_R		0.049
gMVP		0.084
Mutation Taster		=97/3	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;