ENST00000641504.1:c.646C>T

Variant names:

• chr11-75089068-G-A
• rs755101064
• ENST00000641504.1:c.646C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000641504.1(OR2AT4):​c.646C>T​(p.Leu216Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L216V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR2AT4 ENST00000641504.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26339936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR2AT4	NM_001005285.2	c.646C>T	p.Leu216Phe	missense_variant	Exon 2 of 2		NP_001005285.1
OR2AT4	NM_001405852.1	c.646C>T	p.Leu216Phe	missense_variant	Exon 2 of 2		NP_001392781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR2AT4	ENST00000641504.1	c.646C>T	p.Leu216Phe	missense_variant	Exon 2 of 2			ENSP00000493318.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250032 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0019	T;T;T;T;T
Eigen	Benign	-0.059
Eigen_PC	Benign	-0.0090
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.78	.;.;.;.;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.40	N;N;N;N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.010	.;.;.;.;N
REVEL	Benign	0.24
Sift	Benign	0.26	.;.;.;.;T
Sift4G	Benign	0.59	.;.;.;.;T
Polyphen		1.0	D;D;D;D;D
Vest4		0.30
MutPred		0.58		Gain of catalytic residue at L216 (P = 0.0524);Gain of catalytic residue at L216 (P = 0.0524);Gain of catalytic residue at L216 (P = 0.0524);Gain of catalytic residue at L216 (P = 0.0524);Gain of catalytic residue at L216 (P = 0.0524);
MVP		0.27
MPC		0.15
ClinPred		0.50	D
GERP RS		5.1
Varity_R		0.16
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs755101064; hg19: chr11-74800113;