Genetic Variant OR4C46:p.Asp304Asn (chr11-54603089-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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. 8/11 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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.60

Variant links:

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]

OR4C46 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 2641785.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4C46	NM_001004703.1 link	c.910G>A	p.Asp304Asn	missense_variant	Exon 1 of 1	ENST00000328188.1	NP_001004703.1	A6NHA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4C46	ENST00000328188.1 link	c.910G>A	p.Asp304Asn	missense_variant	Exon 1 of 1	6	NM_001004703.1	ENSP00000329056.1		A6NHA9

Frequencies

GnomAD3 genomes

AF:

0.00539

AC:

819

AN:

151838

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00649

AC:

1532

AN:

236004

Hom.:

AF XY:

0.00690

AC XY:

884

AN XY:

128024

show subpopulations

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 SAS exome

AF:

0.00898

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.:

Cov.:

AF XY:

0.00635

AC XY:

4365

AN XY:

687656

show subpopulations

Gnomad4 AFR exome

AF:

0.000808

Gnomad4 AMR exome

AF:

0.00477

Gnomad4 ASJ exome

AF:

0.0130

Gnomad4 EAS exome

AF:

0.0000513

Gnomad4 SAS exome

AF:

0.00978

Gnomad4 FIN exome

AF:

0.00654

Gnomad4 NFE exome

AF:

0.00592

Gnomad4 OTH exome

AF:

0.00630

GnomAD4 genome

AF:

0.00539

AC:

819

AN:

151958

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

444

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00109

Gnomad4 AMR

AF:

0.00841

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00895

Gnomad4 FIN

AF:

0.00842

Gnomad4 NFE

AF:

0.00650

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00459

Hom.:

Bravo

AF:

0.00520

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OR4C46: BS2 -

Computational scores

Source: dbNSFP v4.3

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

LIST_S2

Benign

0.050

MetaRNN

Benign

0.0062

PROVEAN

Benign

0.17

Sift

Benign

0.39

Sift4G

Benign

0.45

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over