chr11-7796119-G-A

Position:

• chr11-7796119-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_153444.1(OR5P2):​c.824C>T​(p.Thr275Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000322 in 1,605,406 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00025 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00033 (12 hom.)
• Consequence: OR5P2 NM_153444.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.54

Genes affected

OR5P2 (HGNC:14783): (olfactory receptor family 5 subfamily P 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]

ENSG00000271758 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022180736).
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR5P2	NM_153444.1	c.824C>T	p.Thr275Ile	missense_variant	1/1	ENST00000329434.3	NP_703145.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR5P2	ENST00000329434.3	c.824C>T	p.Thr275Ile	missense_variant	1/1	6	NM_153444.1	ENSP00000331823.2
ENSG00000271758	ENST00000527565.1	n.542+82888C>T		intron_variant		3
ENSG00000254951	ENST00000529488.5	n.532-41598C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 37 AN: 147814 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0000530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000642

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000413

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000537 AC: 134 AN: 249728 Hom.: 6 AF XY: 0.000548 AC XY: 74 AN XY: 135062

Gnomad AFR exome AF: 0.000261

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00100

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.000329 AC: 480 AN: 1457486 Hom.: 12 Cov.: 35 AF XY: 0.000327 AC XY: 237 AN XY: 725132

Gnomad4 AFR exome AF: 0.0000317

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000362

Gnomad4 FIN exome AF: 0.000524

Gnomad4 NFE exome AF: 0.000359

Gnomad4 OTH exome AF: 0.000349

GnomAD4 genome AF: 0.000250 AC: 37 AN: 147920 Hom.: 4 Cov.: 31 AF XY: 0.000166 AC XY: 12 AN XY: 72262

Gnomad4 AFR AF: 0.0000528

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000642

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.000413

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000412 Hom.: 1

ExAC AF: 0.000845 AC: 102

EpiCase AF: 0.000437

EpiControl AF: 0.000297

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.824C>T (p.T275I) alteration is located in exon 1 (coding exon 1) of the OR5P2 gene. This alteration results from a C to T substitution at nucleotide position 824, causing the threonine (T) at amino acid position 275 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.60
DANN	Benign	0.95
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.10	N
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.071
Sift	Benign	0.052	T
Sift4G	Uncertain	0.048	D
Polyphen		0.012	B
Vest4		0.16
MVP		0.26
MPC		0.0060
ClinPred		0.024	T
GERP RS		-3.4
Varity_R		0.050
gMVP		0.096

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: rs149186820; hg19: chr11-7817666;