ENST00000641504.1:c.786A>G

Variant names:

• chr11-75088928-T-C
• rs1949303597
• NM_001405852.1:c.786A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000641504.1(OR2AT4):​c.786A>G​(p.Ile262Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: OR2AT4 ENST00000641504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.32
• Publications: 0 publications found

Genes affected

OR2AT4 (HGNC:19620): (olfactory receptor family 2 subfamily AT member 4) 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]

ENSG00000284722 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1181556).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641504.1. 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
	OR2AT4	NM_001405852.1	MANE Select	c.786A>G	p.Ile262Met	missense	Exon 2 of 2	NP_001392781.1	A0A126GWB1
	OR2AT4	NM_001005285.2		c.786A>G	p.Ile262Met	missense	Exon 2 of 2	NP_001005285.1	A6NND4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2AT4	ENST00000641504.1	MANE Select	c.786A>G	p.Ile262Met	missense	Exon 2 of 2	ENSP00000493318.1	A6NND4
	OR2AT4	ENST00000305159.3	TSL:6	c.786A>G	p.Ile262Met	missense	Exon 1 of 1	ENSP00000304846.3	A6NND4
	OR2AT4	ENST00000641541.1		c.786A>G	p.Ile262Met	missense	Exon 3 of 3	ENSP00000493299.1	A6NND4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461834 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-1.3
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.060
Sift	Uncertain	0.011	D
Sift4G	Benign	0.12	T
Polyphen		0.72	P
Vest4		0.36
MutPred		0.51		Gain of catalytic residue at S259 (P = 0.2064)
MVP		0.095
MPC		0.11
ClinPred		0.33	T
GERP RS		-1.6
Varity_R		0.15
gMVP		0.10
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1949303597; hg19: chr11-74799973;