11-56664191-G-A

Position:

• chr11-56664191-G-A

Variant summary

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

The NM_001004730.1(OR5AR1):​c.506G>A​(p.Cys169Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00505 in 1,614,020 control chromosomes in the GnomAD database, including 224 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (25 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (199 hom.)
• Consequence: OR5AR1 NM_001004730.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.54

Genes affected

OR5AR1 (HGNC:15260): (olfactory receptor family 5 subfamily AR 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jun 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002196163).
• BP6: Variant 11-56664191-G-A is Benign according to our data. Variant chr11-56664191-G-A is described in ClinVar as [Benign]. Clinvar id is 1291871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5AR1	NM_001004730.1	c.506G>A	p.Cys169Tyr	missense_variant	1/1	ENST00000624596.2	NP_001004730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5AR1	ENST00000624596.2	c.506G>A	p.Cys169Tyr	missense_variant	1/1	6	NM_001004730.1	ENSP00000485240.1

Frequencies

GnomAD3 genomes AF: 0.00605 AC: 919 AN: 152022 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.00102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00957

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.0202

Gnomad FIN AF: 0.00254

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000662

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.0125 AC: 3143 AN: 251360 Hom.: 100 AF XY: 0.0123 AC XY: 1668 AN XY: 135844

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.0174

Gnomad ASJ exome AF: 0.00516

Gnomad EAS exome AF: 0.0941

Gnomad SAS exome AF: 0.0178

Gnomad FIN exome AF: 0.00231

Gnomad NFE exome AF: 0.000889

Gnomad OTH exome AF: 0.00912

GnomAD4 exome AF: 0.00494 AC: 7229 AN: 1461880 Hom.: 199 Cov.: 33 AF XY: 0.00530 AC XY: 3852 AN XY: 727238

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.0167

Gnomad4 ASJ exome AF: 0.00486

Gnomad4 EAS exome AF: 0.0900

Gnomad4 SAS exome AF: 0.0181

Gnomad4 FIN exome AF: 0.00290

Gnomad4 NFE exome AF: 0.000522

Gnomad4 OTH exome AF: 0.00770

GnomAD4 genome AF: 0.00602 AC: 916 AN: 152140 Hom.: 25 Cov.: 32 AF XY: 0.00696 AC XY: 518 AN XY: 74386

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00962

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.0200

Gnomad4 FIN AF: 0.00254

Gnomad4 NFE AF: 0.000662

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00508 Hom.: 43

Bravo AF: 0.00618

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.0121 AC: 1464

Asia WGS AF: 0.0550 AC: 192 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000474

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	Feb 24, 2021	This variant is associated with the following publications: (PMID: 25889363) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Benign	0.46	T
Polyphen		1.0	D
ClinPred		0.071	T
GERP RS		4.8
Varity_R		0.79
gMVP		0.24

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

Other links and lift over

dbSNP: rs79043854; hg19: chr11-56431667; COSMIC: COSV57253029; COSMIC: COSV57253029;