chr7-144259615-A-G

Position:

chr7-144259615-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005328.2(OR2A7):c.14T>C(p.Ile5Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,882 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 0.000053 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OR2A7
NM_001005328.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.798

Variant links:

Genes affected

OR2A7 (HGNC:8234): (olfactory receptor family 2 subfamily A member 7) 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]

OR2A7 links:

ARHGEF34P (HGNC:):

ARHGEF34P links:

ARHGEF35-AS1 (HGNC:41292): (ARHGEF35 antisense RNA 1)

ARHGEF35-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03879127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR2A7	NM_001005328.2 linkuse as main transcript	c.14T>C	p.Ile5Thr	missense_variant	2/2	ENST00000641841.1
ARHGEF34P	NR_033942.1 linkuse as main transcript	n.3585T>C		non_coding_transcript_exon_variant	13/13
ARHGEF35-AS1	NR_126022.1 linkuse as main transcript	n.494-20857A>G		intron_variant, non_coding_transcript_variant
OR2A1-AS1	NR_126023.1 linkuse as main transcript	n.608-19872T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
OR2A7	ENST00000641841.1 linkuse as main transcript	c.14T>C	p.Ile5Thr	missense_variant	2/2		NM_001005328.2	P1
ARHGEF35-AS1	ENST00000460955.5 linkuse as main transcript	n.494-20857A>G		intron_variant, non_coding_transcript_variant		4
OR2A7	ENST00000493325.1 linkuse as main transcript	c.14T>C	p.Ile5Thr	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250520

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.000125

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461120

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151762

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.000194

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

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

Dec 19, 2022

The c.14T>C (p.I5T) alteration is located in exon 1 (coding exon 1) of the OR2A7 gene. This alteration results from a T to C substitution at nucleotide position 14, causing the isoleucine (I) at amino acid position 5 to be replaced by a threonine (T). 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

0.093

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.0

DANN

Benign

0.74

DEOGEN2

Benign

0.0021

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0087

M_CAP

Benign

0.0010

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.34

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

1.3

.;N

REVEL

Benign

0.033

Sift

Benign

0.030

.;D

Sift4G

Benign

0.24

.;T

Polyphen

0.0

B;B

Vest4

0.067

MVP

0.030

ClinPred

0.022

GERP RS

-3.1

Varity_R

0.033

gMVP

0.087

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