chr14-21665161-T-A

Variant names:

• chr14-21665161-T-A
• rs368602495
• NM_001001912.3:c.79T>A

Variant summary

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

The NM_001001912.3(OR4E2):​c.79T>A​(p.Phe27Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000651 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: OR4E2 NM_001001912.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.512
• Publications: 1 publications found

Genes affected

OR4E2 (HGNC:8297): (olfactory receptor family 4 subfamily E 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]

TRA (HGNC:12027):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.022403926).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001912.3. 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
	OR4E2	NM_001001912.3	MANE Select	c.79T>A	p.Phe27Ile	missense	Exon 4 of 4	NP_001001912.2	A0A126GVR8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR4E2	ENST00000641524.1	MANE Select	c.79T>A	p.Phe27Ile	missense	Exon 4 of 4	ENSP00000493386.1	A0A126GVR8

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000749

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.0000521 AC: 13 AN: 249396 AF XY: 0.0000517

Gnomad AFR exome AF: 0.000839

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000458 AC: 67 AN: 1461754 Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32 AN XY: 727194

African (AFR) AF: 0.00131 AC: 44 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111914

Other (OTH) AF: 0.000348 AC: 21 AN: 60392

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152246 Hom.: 0 Cov.: 32 AF XY: 0.000201 AC XY: 15 AN XY: 74460

African (AFR) AF: 0.000794 AC: 33 AN: 41536

American (AMR) AF: 0.000327 AC: 5 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000306

ESP6500AA AF: 0.00104 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000497 AC: 6

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	-0.51	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.4
DANN	Benign	0.86
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.51
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.092
Sift	Benign	0.34	T
Sift4G	Benign	0.23	T
Vest4		0.45
MVP		0.014
MPC		0.021
ClinPred		0.016	T
GERP RS		2.7
gMVP		0.31
Mutation Taster		=98/2	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: rs368602495; hg19: chr14-22133375;