11-4586973-A-C

Variant names:

• chr11-4586973-A-C
• rs142676846
• NM_001405760.1:c.83A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001405760.1(OR52I2):​c.83A>C​(p.His28Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: OR52I2 NM_001405760.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.818
• Publications: 1 publications found

Genes affected

OR52I2 (HGNC:15221): (olfactory receptor family 52 subfamily I 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13880709).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001405760.1. 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
	OR52I2	NM_001405760.1	MANE Select	c.83A>C	p.His28Pro	missense	Exon 2 of 2	NP_001392689.1	A0A126GWK8
	OR52I2	NM_001005170.4		c.83A>C	p.His28Pro	missense	Exon 1 of 1	NP_001005170.2	A0A126GWK8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR52I2	ENST00000641896.1	MANE Select	c.83A>C	p.His28Pro	missense	Exon 2 of 2	ENSP00000493402.1	A0A126GWK8
	OR52I2	ENST00000641486.1		c.83A>C	p.His28Pro	missense	Exon 1 of 1	ENSP00000493314.1	A0A126GWK8

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000290

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000676 AC: 17 AN: 251356 AF XY: 0.0000368

Gnomad AFR exome AF: 0.000861

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461854 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 727232

African (AFR) AF: 0.000418 AC: 14 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111978

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74328

African (AFR) AF: 0.000290 AC: 12 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000839 Hom.: 0

Bravo AF: 0.000117

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.82
PrimateAI	Benign	0.24	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.17
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.012	D
Polyphen		0.061	B
Vest4		0.58
MVP		0.27
MPC		0.28
ClinPred		0.050	T
GERP RS		4.1
PromoterAI		0.0065	Neutral
Varity_R		0.91
gMVP		0.78
Mutation Taster		=94/6	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: rs142676846; hg19: chr11-4608203;