11-6169764-C-G

Variant names:

• chr11-6169764-C-G
• rs745410447
• NM_001004052.1:c.563G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001004052.1(OR52B2):​c.563G>C​(p.Arg188Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R188H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR52B2 NM_001004052.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• Publications: 3 publications found

Genes affected

OR52B2 (HGNC:15207): (olfactory receptor family 52 subfamily B member 2) 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]

ENSG00000254444 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004867196).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004052.1. 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
	OR52B2	NM_001004052.1	MANE Select	c.563G>C	p.Arg188Pro	missense	Exon 1 of 1	NP_001004052.1	Q96RD2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52B2	ENST00000530810.2	TSL:6 MANE Select	c.563G>C	p.Arg188Pro	missense	Exon 1 of 1	ENSP00000432011.1	Q96RD2
	ENSG00000254444	ENST00000529961.1	TSL:5	n.286+15527G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151676 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000443

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0107 AC: 2100 AN: 196782 AF XY: 0.0103

Gnomad AFR exome AF: 0.0192

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.0174

Gnomad FIN exome AF: 0.0126

Gnomad NFE exome AF: 0.0115

Gnomad OTH exome AF: 0.00448

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00104 AC: 1492 AN: 1427836 Hom.: 0 Cov.: 33 AF XY: 0.00112 AC XY: 793 AN XY: 708036

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00283 AC: 91 AN: 32166

American (AMR) AF: 0.00805 AC: 313 AN: 38858

Ashkenazi Jewish (ASJ) AF: 0.000279 AC: 7 AN: 25118

East Asian (EAS) AF: 0.00528 AC: 195 AN: 36900

South Asian (SAS) AF: 0.00136 AC: 112 AN: 82536

European-Finnish (FIN) AF: 0.00385 AC: 184 AN: 47736

Middle Eastern (MID) AF: 0.00115 AC: 6 AN: 5226

European-Non Finnish (NFE) AF: 0.000492 AC: 541 AN: 1100078

Other (OTH) AF: 0.000726 AC: 43 AN: 59218

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000264 AC: 4 AN: 151784 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74188

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41404

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67754

Other (OTH) AF: 0.00 AC: 0 AN: 2098

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00105 Hom.: 0

ExAC AF: 0.0162 AC: 1956

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0091	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		-0.49
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.22
MPC		0.24
ClinPred		0.069	T
GERP RS		5.0
Varity_R		0.80
gMVP		0.74
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs745410447; hg19: chr11-6190994; COSMIC: COSV73209206;