chr11-5841212-A-C

Variant names:

• chr11-5841212-A-C
• rs142759166
• NM_001005167.2:c.686T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001005167.2(OR52E6):​c.686T>G​(p.Leu229Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000984 in 1,613,970 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L229V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0054 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (9 hom.)
• Consequence: OR52E6 NM_001005167.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.61
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006006807).
• BP6: Variant 11-5841212-A-C is Benign according to our data. Variant chr11-5841212-A-C is described in ClinVar as Benign. ClinVar VariationId is 723591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00538 (820/152312) while in subpopulation AFR AF = 0.0188 (783/41568). AF 95% confidence interval is 0.0177. There are 6 homozygotes in GnomAd4. There are 373 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005167.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52E6	NM_001005167.2	MANE Select	c.686T>G	p.Leu229Arg	missense	Exon 1 of 1	NP_001005167.1	A0A126GVK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52E6	ENST00000329322.5	TSL:6 MANE Select	c.686T>G	p.Leu229Arg	missense	Exon 1 of 1	ENSP00000328878.5	Q96RD3
	TRIM5	ENST00000412903.1	TSL:1	c.-62+96189T>G		intron	N/A	ENSP00000388031.1	E7EQQ5
	OR52E6	ENST00000379946.2	TSL:6	c.698T>G	p.Leu233Arg	missense	Exon 2 of 2	ENSP00000369279.2	J3KPH0

Frequencies

GnomAD3 genomes AF: 0.00538 AC: 819 AN: 152194 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00129 AC: 323 AN: 249562 AF XY: 0.000851

Gnomad AFR exome AF: 0.0192

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000525 AC: 768 AN: 1461658 Hom.: 9 Cov.: 32 AF XY: 0.000406 AC XY: 295 AN XY: 727100

African (AFR) AF: 0.0192 AC: 644 AN: 33478

American (AMR) AF: 0.000582 AC: 26 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111942

Other (OTH) AF: 0.00128 AC: 77 AN: 60390

GnomAD4 genome AF: 0.00538 AC: 820 AN: 152312 Hom.: 6 Cov.: 32 AF XY: 0.00501 AC XY: 373 AN XY: 74484

African (AFR) AF: 0.0188 AC: 783 AN: 41568

American (AMR) AF: 0.00131 AC: 20 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68032

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00258 Hom.: 1

Bravo AF: 0.00589

ESP6500AA AF: 0.0157 AC: 69

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00161 AC: 195

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	0.043
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	4.0	H
PhyloP100		2.6
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.045
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.54
MVP		0.33
MPC		0.026
ClinPred		0.15	T
GERP RS		3.5
Varity_R		0.89
gMVP		0.14
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142759166; hg19: chr11-5862442;