11-54603251-C-G

Variant names:

• chr11-54603251-C-G
• rs150447323
• NM_001004703.1:c.748G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001004703.1(OR4C46):​c.748G>C​(p.Val250Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,612,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/11 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000054 (0 hom.)
• Consequence: OR4C46 NM_001004703.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 1 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06833726).

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.748G>C	p.Val250Leu	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.748G>C	p.Val250Leu	missense	Exon 1 of 1	ENSP00000329056.1	A6NHA9

Frequencies

GnomAD3 genomes AF: 0.000612 AC: 93 AN: 151932 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000199 AC: 50 AN: 250978 AF XY: 0.000162

Gnomad AFR exome AF: 0.00277

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000541 AC: 79 AN: 1460942 Hom.: 0 Cov.: 40 AF XY: 0.0000495 AC XY: 36 AN XY: 726850

African (AFR) AF: 0.00200 AC: 67 AN: 33456

American (AMR) AF: 0.0000895 AC: 4 AN: 44714

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111188

Other (OTH) AF: 0.0000994 AC: 6 AN: 60360

GnomAD4 genome AF: 0.000612 AC: 93 AN: 152050 Hom.: 0 Cov.: 30 AF XY: 0.000565 AC XY: 42 AN XY: 74288

African (AFR) AF: 0.00217 AC: 90 AN: 41496

American (AMR) AF: 0.000196 AC: 3 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5114

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.000684

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.75
CADD	Benign	19
DANN	Benign	0.71
DEOGEN2	Benign	0.012	T
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.068	T
PhyloP100		-0.072
PROVEAN	Benign	-2.2	N
Sift	Uncertain	0.017	D
Sift4G	Benign	0.19	T
Vest4		0.087
gMVP		0.74

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: rs150447323; hg19: chr11-51516029;