11-54603089-C-T

Variant names:

• chr11-54603089-C-T
• rs140000110
• NM_001004703.1:c.910G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001004703.1(OR4C46):​c.910G>A​(p.Asp304Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00597 in 1,530,922 control chromosomes in the GnomAD database, including 36 homozygotes. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (2 hom., cov: 28)
  • Exomes 𝑓: 0.0060 (34 hom.)
• Consequence: OR4C46 NM_001004703.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60
• Publications: 7 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0062384605).
• BP6: Variant 11-54603089-C-T is Benign according to our data. Variant chr11-54603089-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2641785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.910G>A	p.Asp304Asn	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.910G>A	p.Asp304Asn	missense	Exon 1 of 1	ENSP00000329056.1	A6NHA9

Frequencies

GnomAD3 genomes AF: 0.00539 AC: 819 AN: 151838 Hom.: 2 Cov.: 28

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00849

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00874

Gnomad FIN AF: 0.00842

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00650

Gnomad OTH AF: 0.00814

GnomAD2 exomes AF: 0.00649 AC: 1532 AN: 236004 AF XY: 0.00690

Gnomad AFR exome AF: 0.00153

Gnomad AMR exome AF: 0.00456

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00738

Gnomad NFE exome AF: 0.00735

Gnomad OTH exome AF: 0.00763

GnomAD4 exome AF: 0.00603 AC: 8321 AN: 1378964 Hom.: 34 Cov.: 25 AF XY: 0.00635 AC XY: 4365 AN XY: 687656

African (AFR) AF: 0.000808 AC: 26 AN: 32182

American (AMR) AF: 0.00477 AC: 204 AN: 42724

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 316 AN: 24270

East Asian (EAS) AF: 0.0000513 AC: 2 AN: 39000

South Asian (SAS) AF: 0.00978 AC: 808 AN: 82638

European-Finnish (FIN) AF: 0.00654 AC: 329 AN: 50276

Middle Eastern (MID) AF: 0.0165 AC: 91 AN: 5518

European-Non Finnish (NFE) AF: 0.00592 AC: 6184 AN: 1045048

Other (OTH) AF: 0.00630 AC: 361 AN: 57308

GnomAD4 genome AF: 0.00539 AC: 819 AN: 151958 Hom.: 2 Cov.: 28 AF XY: 0.00598 AC XY: 444 AN XY: 74286

African (AFR) AF: 0.00109 AC: 45 AN: 41470

American (AMR) AF: 0.00841 AC: 128 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5150

South Asian (SAS) AF: 0.00895 AC: 43 AN: 4802

European-Finnish (FIN) AF: 0.00842 AC: 89 AN: 10574

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00650 AC: 442 AN: 67964

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00521 Hom.: 0

Bravo AF: 0.00520

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.72
DEOGEN2	Benign	0.0034	T
LIST_S2	Benign	0.050	T
MetaRNN	Benign	0.0062	T
PhyloP100		-1.6
PROVEAN	Benign	0.17	N
Sift	Benign	0.39	T
Sift4G	Benign	0.45	T
Vest4		0.13
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs140000110; hg19: chr11-51516191;