dbSNP rs75219695: OR4D11:p.Ala143Gly (chr11-59504003-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001004706.1(OR4D11):c.428C>G(p.Ala143Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,613,998 control chromosomes in the GnomAD database, including 252 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. A143V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.022 ( 119 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 133 hom. )

Consequence

OR4D11
NM_001004706.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.812

Variant links:

Genes affected

OR4D11 (HGNC:15174): (olfactory receptor family 4 subfamily D member 11) 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]

OR4D11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002837211).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR4D11	NM_001004706.1 link	c.428C>G	p.Ala143Gly	missense_variant	Exon 1 of 1	ENST00000313253.1	NP_001004706.1	Q8NGI4A0A126GVQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR4D11	ENST00000313253.1 link	c.428C>G	p.Ala143Gly	missense_variant	Exon 1 of 1	6	NM_001004706.1	ENSP00000320077.1		Q8NGI4

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3367

AN:

152154

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0780

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00559

AC:

1405

AN:

251278

Hom.:

AF XY:

0.00395

AC XY:

537

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.0770

Gnomad AMR exome

AF:

0.00327

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00227

AC:

3323

AN:

1461726

Hom.:

133

Cov.:

AF XY:

0.00199

AC XY:

1450

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0811

Gnomad4 AMR exome

AF:

0.00362

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000123

Gnomad4 OTH exome

AF:

0.00440

GnomAD4 genome

AF:

0.0222

AC:

3377

AN:

152272

Hom.:

119

Cov.:

AF XY:

0.0207

AC XY:

1538

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0780

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.0254

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0741

AC:

326

ESP6500EA

AF:

0.000815

AC:

ExAC

AF:

0.00680

AC:

826

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.23

DANN

Benign

0.53

DEOGEN2

Benign

0.0062

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.018

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.52

PrimateAI

Benign

0.25

PROVEAN

Benign

1.2

REVEL

Benign

0.065

Sift

Benign

1.0

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.10

MVP

0.23

MPC

0.013

ClinPred

0.0062

GERP RS

2.2

Varity_R

0.038

gMVP

0.075

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over