11-5841501-A-G

Position:

• chr11-5841501-A-G

Variant summary

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

The NM_001005167.2(OR52E6):​c.397T>C​(p.Trp133Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,613,228 control chromosomes in the GnomAD database, including 192,407 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 0.43 (14918 hom., cov: 33)
  • Exomes 𝑓: 0.49 (177489 hom.)
• Consequence: OR52E6 NM_001005167.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.531

Genes affected

OR52E6 (HGNC:15215): (olfactory receptor family 52 subfamily E member 6) 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]

TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.8002305E-5).
• BP6: Variant 11-5841501-A-G is Benign according to our data. Variant chr11-5841501-A-G is described in ClinVar as [Benign]. Clinvar id is 768422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR52E6	NM_001005167.2	c.397T>C	p.Trp133Arg	missense_variant	1/1	ENST00000329322.5	NP_001005167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR52E6	ENST00000329322.5	c.397T>C	p.Trp133Arg	missense_variant	1/1	6	NM_001005167.2	ENSP00000328878.5
TRIM5	ENST00000412903.1	c.-62+95900T>C		intron_variant		1		ENSP00000388031.1
OR52E6	ENST00000379946.2	c.409T>C	p.Trp137Arg	missense_variant	2/2	6		ENSP00000369279.2
TRIM5	ENST00000380027.5	c.-441+14251T>C		intron_variant		5		ENSP00000369366.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65401 AN: 151986 Hom.: 14918 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.434

GnomAD3 exomes AF: 0.461 AC: 115540 AN: 250822 Hom.: 27244 AF XY: 0.463 AC XY: 62740 AN XY: 135516

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.470

Gnomad SAS exome AF: 0.398

Gnomad FIN exome AF: 0.515

Gnomad NFE exome AF: 0.505

Gnomad OTH exome AF: 0.471

GnomAD4 exome AF: 0.490 AC: 716060 AN: 1461124 Hom.: 177489 Cov.: 73 AF XY: 0.488 AC XY: 354902 AN XY: 726906

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.455

Gnomad4 EAS exome AF: 0.466

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.514

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.473

GnomAD4 genome AF: 0.430 AC: 65412 AN: 152104 Hom.: 14918 Cov.: 33 AF XY: 0.430 AC XY: 31929 AN XY: 74326

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.437

Alfa AF: 0.447 Hom.: 6466

Bravo AF: 0.418

ESP6500AA AF: 0.274 AC: 1206

ESP6500EA AF: 0.505 AC: 4339

ExAC AF: 0.456 AC: 55313

EpiCase AF: 0.498

EpiControl AF: 0.500

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 25, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.13
DANN	Benign	0.70
DEOGEN2	Benign	0.0016	T;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.032	T;T
MetaRNN	Benign	0.000018	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	-3.2	N;.
PrimateAI	Benign	0.17	T
PROVEAN	Benign	5.8	N;N
REVEL	Benign	0.082
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.019
MutPred		0.22		Loss of catalytic residue at M136 (P = 0.0038);.;
MPC		0.0050
ClinPred		0.017	T
GERP RS		-6.9
Varity_R		0.051
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10838719; hg19: chr11-5862731;