Variant chr11-75089392-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001005285.2(OR2AT4):c.322C>A(p.Leu108Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 1,614,100 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 5 hom. )

Consequence

OR2AT4
NM_001005285.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

Variant links:

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]

OR2AT4 links:

ENSG00000284722 (HGNC:):

ENSG00000284722 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012199938).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR2AT4	NM_001005285.2 link	c.322C>A	p.Leu108Ile	missense_variant	2/2		NP_001005285.1	A6NND4A0A126GWB1
OR2AT4	NM_001405852.1 link	c.322C>A	p.Leu108Ile	missense_variant	2/2		NP_001392781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR2AT4	ENST00000641504.1 link	c.322C>A	p.Leu108Ile	missense_variant	2/2			ENSP00000493318.1		A6NND4

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

163

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00178

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00115

AC:

288

AN:

251294

Hom.:

AF XY:

0.00112

AC XY:

152

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000810

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.00197

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00219

AC:

3201

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

1564

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000850

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.00265

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.00107

AC:

163

AN:

152242

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00178

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00124

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000988

AC:

120

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.322C>A (p.L108I) alteration is located in exon 1 (coding exon 1) of the OR2AT4 gene. This alteration results from a C to A substitution at nucleotide position 322, causing the leucine (L) at amino acid position 108 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

0.13

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0021

T;T;T;T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.096

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.68

.;.;.;.;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.012

T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.1

L;L;L;L;L

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.30

.;.;.;.;N

REVEL

Benign

0.089

Sift

Benign

0.28

.;.;.;.;T

Sift4G

Benign

0.17

.;.;.;.;T

Polyphen

0.87

P;P;P;P;P

Vest4

0.26

MVP

0.12

MPC

0.11

ClinPred

0.051

GERP RS

2.9

Varity_R

0.078

gMVP

0.050

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over