11-59443715-G-A

Position:

• chr11-59443715-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.61 (29424 hom., cov: 29)
  • Exomes 𝑓: 0.67 (328065 hom.)
• Consequence: OR5A1 NM_001004728.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 8.07

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]

ACMG classification

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	c.547G>A	p.Asp183Asn	missense_variant	2/2	ENST00000641045.1	NP_001004728.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93233 AN: 151642 Hom.: 29432 Cov.: 29

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

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.: 68 AF XY: 0.672 AC XY: 488535 AN XY: 727176

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.: 29 AF XY: 0.618 AC XY: 45831 AN XY: 74160

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

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	T
BayesDel_noAF	Benign	-0.52
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.017	T;T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	.;T
MetaRNN	Benign	0.0000047	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Benign	0.35	T
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	T
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

Other links and lift over

dbSNP: rs6591536; hg19: chr11-59211188; COSMIC: COSV57376990;