7-144259372-T-A

Position:

chr7-144259372-T-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005328.2(OR2A7):c.257A>T(p.His86Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.0016 ( 0 hom., cov: 19)

Exomes 𝑓: 0.00070 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

OR2A7
NM_001005328.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.27

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03725314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
OR2A7	NM_001005328.2 linkuse as main transcript	c.257A>T	p.His86Leu	missense_variant	2/2	ENST00000641841.1
ARHGEF34P	NR_033942.1 linkuse as main transcript	n.3828A>T		non_coding_transcript_exon_variant	13/13
ARHGEF35-AS1	NR_126022.1 linkuse as main transcript	n.494-21100T>A		intron_variant, non_coding_transcript_variant
OR2A1-AS1	NR_126023.1 linkuse as main transcript	n.608-19629A>T		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.257A>T	p.His86Leu	missense_variant	2/2		NM_001005328.2	P1
ARHGEF35-AS1	ENST00000460955.5 linkuse as main transcript	n.494-21100T>A		intron_variant, non_coding_transcript_variant		4
OR2A7	ENST00000493325.1 linkuse as main transcript	c.257A>T	p.His86Leu	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

196

AN:

125984

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00505

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00163

Gnomad EAS

AF:

0.000207

Gnomad SAS

AF:

0.000805

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00373

Gnomad NFE

AF:

0.000411

Gnomad OTH

AF:

0.00123

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000703

AC:

731

AN:

1040194

Hom.:

Cov.:

AF XY:

0.000677

AC XY:

357

AN XY:

527372

show subpopulations

Gnomad4 AFR exome

AF:

0.0101

Gnomad4 AMR exome

AF:

0.000780

Gnomad4 ASJ exome

AF:

0.00285

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000248

Gnomad4 FIN exome

AF:

0.0000216

Gnomad4 NFE exome

AF:

0.000454

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00155

AC:

196

AN:

126084

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

AN XY:

60642

show subpopulations

Gnomad4 AFR

AF:

0.00503

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00163

Gnomad4 EAS

AF:

0.000208

Gnomad4 SAS

AF:

0.000806

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000411

Gnomad4 OTH

AF:

0.00121

Alfa

AF:

0.00294

Hom.:

ExAC

AF:

0.0000176

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

Mar 07, 2023

The c.257A>T (p.H86L) alteration is located in exon 1 (coding exon 1) of the OR2A7 gene. This alteration results from a A to T substitution at nucleotide position 257, causing the histidine (H) at amino acid position 86 to be replaced by a leucine (L). 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

0.083

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.1

DANN

Benign

0.80

DEOGEN2

Benign

0.0056

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.010

M_CAP

Benign

0.0013

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.47

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.7

.;N

REVEL

Benign

0.029

Sift

Benign

0.23

.;T

Sift4G

Benign

0.24

.;T

Polyphen

0.0

B;B

Vest4

0.12

MutPred

0.28

Loss of methylation at K89 (P = 0.0617);Loss of methylation at K89 (P = 0.0617);

MVP

0.16

ClinPred

0.0011

GERP RS

-2.4

Varity_R

0.085

gMVP

0.15

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

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