Variant 11-55820134-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001001952.1(OR5D18):c.505T>A(p.Phe169Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,613,950 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00085 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

OR5D18
NM_001001952.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

OR5D18 (HGNC:15285): (olfactory receptor family 5 subfamily D member 18) 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]

OR5D18 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13046214).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR5D18	NM_001001952.1 linkuse as main transcript	c.505T>A	p.Phe169Ile	missense_variant	1/1	ENST00000333976.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR5D18	ENST00000333976.7 linkuse as main transcript	c.505T>A	p.Phe169Ile	missense_variant	1/1		NM_001001952.1	P1

Frequencies

GnomAD3 genomes

AF:

0.000856

AC:

130

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000851

AC:

214

AN:

251448

Hom.:

AF XY:

0.000935

AC XY:

127

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.00153

AC:

2236

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

1140

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000783

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00112

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00179

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.000848

AC:

129

AN:

152076

Hom.:

Cov.:

AF XY:

0.000753

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00146

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.000952

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000815

AC:

ExAC

AF:

0.000865

AC:

105

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00169

EpiControl

AF:

0.00154

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2022

The c.505T>A (p.F169I) alteration is located in exon 1 (coding exon 1) of the OR5D18 gene. This alteration results from a T to A substitution at nucleotide position 505, causing the phenylalanine (F) at amino acid position 169 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.55

M_CAP

Benign

0.0017

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

0.56

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.16

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.46

MVP

0.61

MPC

0.38

ClinPred

0.074

GERP RS

4.8

Varity_R

0.59

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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