11-54603251-C-A

Variant names:

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

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>T​(p.Val250Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,612,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: OR4C46 NM_001004703.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.0986487).

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>T	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>T	p.Val250Leu	missense	Exon 1 of 1	ENSP00000329056.1	A6NHA9

Frequencies

GnomAD3 genomes AF: 0.000178 AC: 27 AN: 151932 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00144

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250978 AF XY: 0.0000369

Gnomad AFR exome AF: 0.000554

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1460946 Hom.: 0 Cov.: 40 AF XY: 0.0000124 AC XY: 9 AN XY: 726852

African (AFR) AF: 0.000568 AC: 19 AN: 33460

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 53418

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

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

Other (OTH) AF: 0.0000166 AC: 1 AN: 60360

GnomAD4 genome AF: 0.000178 AC: 27 AN: 151932 Hom.: 0 Cov.: 30 AF XY: 0.000162 AC XY: 12 AN XY: 74160

African (AFR) AF: 0.000580 AC: 24 AN: 41374

American (AMR) AF: 0.00 AC: 0 AN: 15256

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00144 AC: 3 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Benign	0.73
DEOGEN2	Benign	0.012	T
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.099	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)		0.010		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; COSMIC: COSV100060700;