rs200877558

Positions:

• chr1-248273336-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001004695.2(OR2T33):​c.479T>C​(p.Val160Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.039 (17 hom., cov: 33)
  • Exomes 𝑓: 0.24 (66 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR2T33 NM_001004695.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73

Genes affected

OR2T33 (HGNC:31255): (olfactory receptor family 2 subfamily T member 33) 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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024973452).
• BP6: Variant 1-248273336-A-G is Benign according to our data. Variant chr1-248273336-A-G is described in ClinVar as [Benign]. Clinvar id is 403272.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR2T33	NM_001004695.2	c.479T>C	p.Val160Ala	missense_variant	2/2	ENST00000641220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR2T33	ENST00000641220.1	c.479T>C	p.Val160Ala	missense_variant	2/2		NM_001004695.2	P1
OR2T33	ENST00000318021.4	c.479T>C	p.Val160Ala	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4268 AN: 110592 Hom.: 16 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.0554

Gnomad AMI AF: 0.0111

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0261

Gnomad EAS AF: 0.00915

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.0413

Gnomad MID AF: 0.0340

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.0414

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.244 AC: 211383 AN: 865754 Hom.: 66 Cov.: 121 AF XY: 0.235 AC XY: 101799 AN XY: 432548

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.0289

Gnomad4 SAS exome AF: 0.0849

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0387 AC: 4279 AN: 110664 Hom.: 17 Cov.: 33 AF XY: 0.0408 AC XY: 2202 AN XY: 53960

Gnomad4 AFR AF: 0.0555

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0261

Gnomad4 EAS AF: 0.00919

Gnomad4 SAS AF: 0.0248

Gnomad4 FIN AF: 0.0413

Gnomad4 NFE AF: 0.0331

Gnomad4 OTH AF: 0.0410

Alfa AF: 0.180 Hom.: 2

ExAC AF: 0.388 AC: 47132

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.35
DANN	Benign	0.22
DEOGEN2	Benign	0.0066	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0087	N
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.33	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
Polyphen		0.0	B;B
Vest4		0.056
MPC		1.3
ClinPred		0.0030	T
GERP RS		-2.8
Varity_R		0.037
gMVP		0.13

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: rs200877558; hg19: chr1-248436638; COSMIC: COSV58813722;