Variant 11-5967825-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001146033.1(OR56A5):c.670A>G(p.Ile224Val) variant causes a missense change. The variant allele was found at a frequency of 0.000304 in 1,565,686 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

OR56A5
NM_001146033.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

Variant links:

Genes affected

OR56A5 (HGNC:14792): (olfactory receptor family 56 subfamily A member 5) 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, Mar 2009]

OR56A5 links:

OR56A3 (HGNC:):

OR56A3 links:

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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=0.035336047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR56A5	NM_001146033.1 linkuse as main transcript	c.670A>G	p.Ile224Val	missense_variant	1/1	ENST00000532411.2
OR56A3	XM_047426926.1 linkuse as main transcript	c.*468+19063T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR56A5	ENST00000532411.2 linkuse as main transcript	c.670A>G	p.Ile224Val	missense_variant	1/1		NM_001146033.1	P1

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000918

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000284

AC:

AN:

175888

Hom.:

AF XY:

0.000301

AC XY:

AN XY:

92936

show subpopulations

Gnomad AFR exome

AF:

0.000101

Gnomad AMR exome

AF:

0.000851

Gnomad ASJ exome

AF:

0.000115

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000415

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000308

Gnomad OTH exome

AF:

0.000622

GnomAD4 exome

AF:

0.000303

AC:

428

AN:

1413500

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

218

AN XY:

698390

show subpopulations

Gnomad4 AFR exome

AF:

0.000433

Gnomad4 AMR exome

AF:

0.000842

Gnomad4 ASJ exome

AF:

0.000237

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000868

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000285

Gnomad4 OTH exome

AF:

0.000750

GnomAD4 genome

AF:

0.000315

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000210

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.000227

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

Jun 22, 2023

The c.670A>G (p.I224V) alteration is located in exon 1 (coding exon 1) of the OR56A5 gene. This alteration results from a A to G substitution at nucleotide position 670, causing the isoleucine (I) at amino acid position 224 to be replaced by a valine (V). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.017

.;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.035

T;T

MutationAssessor

Pathogenic

4.1

.;H

PrimateAI

Benign

0.38

Sift4G

Uncertain

0.022

D;D

Polyphen

1.0

.;D

Vest4

0.61

MVP

0.35

GERP RS

4.9

Varity_R

0.049

gMVP

0.33

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