11-54603094-C-T

Variant names:

• chr11-54603094-C-T
• rs142620784
• NM_001004703.1:c.905G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004703.1(OR4C46):​c.905G>A​(p.Arg302Lys) 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. 7/11 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. R302T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR4C46 NM_001004703.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 2 publications found

Genes affected

OR4C46 (HGNC:31271): (olfactory receptor family 4 subfamily C member 46) 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063403934).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004703.1. 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
	OR4C46	NM_001004703.1	MANE Select	c.905G>A	p.Arg302Lys	missense	Exon 1 of 1	NP_001004703.1	A6NHA9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4C46	ENST00000328188.1	TSL:6 MANE Select	c.905G>A	p.Arg302Lys	missense	Exon 1 of 1	ENSP00000329056.1	A6NHA9

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1384790 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 690666

African (AFR) AF: 0.00 AC: 0 AN: 32270

American (AMR) AF: 0.00 AC: 0 AN: 42818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24324

East Asian (EAS) AF: 0.00 AC: 0 AN: 39054

South Asian (SAS) AF: 0.00 AC: 0 AN: 82754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1049902

Other (OTH) AF: 0.00 AC: 0 AN: 57526

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.28
DANN	Benign	0.45
DEOGEN2	Benign	0.0015	T
LIST_S2	Benign	0.028	T
MetaRNN	Benign	0.063	T
PhyloP100		-1.7
PROVEAN	Benign	-0.66	N
Sift	Benign	0.45	T
Sift4G	Benign	0.62	T
Vest4		0.11
gMVP		0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs142620784; hg19: chr11-51516186;