Variant chr11-59443715-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001004728.2(OR5A1):c.547G>A(p.Asp183Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.663 in 1,613,526 control chromosomes in the GnomAD database, including 357,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.61 ( 29424 hom., cov: 29)

Exomes 𝑓: 0.67 ( 328065 hom. )

Consequence

OR5A1
NM_001004728.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.07

Variant links:

Genes affected

OR5A1 (HGNC:8319): (olfactory receptor family 5 subfamily A member 1) 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]

OR5A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.7326585E-6).

BP6

Variant 11-59443715-G-A is Benign according to our data. Variant chr11-59443715-G-A is described in ClinVar as [Benign]. Clinvar id is 1245803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5A1	NM_001004728.2 link	c.547G>A	p.Asp183Asn	missense_variant	2/2	ENST00000641045.1	NP_001004728.1	Q8NGJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5A1	ENST00000641045.1 link	c.547G>A	p.Asp183Asn	missense_variant	2/2		NM_001004728.2	ENSP00000493195.1		Q8NGJ0

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93233

AN:

151642

Hom.:

29432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.768

Gnomad AMR

AF:

0.595

Gnomad ASJ

AF:

0.707

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.747

Gnomad FIN

AF:

0.664

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.673

Gnomad OTH

AF:

0.627

GnomAD3 exomes

AF:

0.658

AC:

165324

AN:

251126

Hom.:

55309

AF XY:

0.669

AC XY:

90827

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.469

Gnomad AMR exome

AF:

0.555

Gnomad ASJ exome

AF:

0.708

Gnomad EAS exome

AF:

0.753

Gnomad SAS exome

AF:

0.747

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.671

Gnomad OTH exome

AF:

0.667

GnomAD4 exome

AF:

0.668

AC:

976617

AN:

1461766

Hom.:

328065

Cov.:

AF XY:

0.672

AC XY:

488535

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.461

Gnomad4 AMR exome

AF:

0.559

Gnomad4 ASJ exome

AF:

0.698

Gnomad4 EAS exome

AF:

0.707

Gnomad4 SAS exome

AF:

0.744

Gnomad4 FIN exome

AF:

0.672

Gnomad4 NFE exome

AF:

0.670

Gnomad4 OTH exome

AF:

0.672

GnomAD4 genome

AF:

0.615

AC:

93264

AN:

151760

Hom.:

29424

Cov.:

AF XY:

0.618

AC XY:

45831

AN XY:

74160

show subpopulations

Gnomad4 AFR

AF:

0.469

Gnomad4 AMR

AF:

0.594

Gnomad4 ASJ

AF:

0.707

Gnomad4 EAS

AF:

0.742

Gnomad4 SAS

AF:

0.746

Gnomad4 FIN

AF:

0.664

Gnomad4 NFE

AF:

0.673

Gnomad4 OTH

AF:

0.627

Alfa

AF:

0.665

Hom.:

86166

Bravo

AF:

0.602

TwinsUK

AF:

0.669

AC:

2482

ALSPAC

AF:

0.674

AC:

2598

ESP6500AA

AF:

0.479

AC:

2109

ESP6500EA

AF:

0.673

AC:

5785

ExAC

AF:

0.660

AC:

80121

Asia WGS

AF:

0.675

AC:

2349

AN:

3478

EpiCase

AF:

0.667

EpiControl

AF:

0.671

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2020	This variant is associated with the following publications: (PMID: 23910657) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.017

T;T

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

.;T

MetaRNN

Benign

0.0000047

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;M

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-5.0

.;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.026

.;D

Sift4G

Uncertain

0.024

.;D

Polyphen

1.0

D;D

Vest4

0.17

MPC

0.20

ClinPred

0.018

GERP RS

6.0

Varity_R

0.59

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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