Variant chr8-166370-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001005504.1(OR4F21):c.655G>A(p.Val219Ile) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.073 ( 1 hom., cov: 4)

Exomes 𝑓: 0.047 ( 341 hom. )

Failed GnomAD Quality Control

Consequence

OR4F21
NM_001005504.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.18

Variant links:

Genes affected

OR4F21 (HGNC:19583): (olfactory receptor family 4 subfamily F member 21) 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]

OR4F21 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034701735).

BP6

Variant 8-166370-C-T is Benign according to our data. Variant chr8-166370-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2343404.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR4F21	NM_001005504.1 linkuse as main transcript	c.655G>A	p.Val219Ile	missense_variant	1/1	ENST00000320901.4	NP_001005504.1	O95013

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR4F21	ENST00000320901.4 linkuse as main transcript	c.655G>A	p.Val219Ile	missense_variant	1/1	6	NM_001005504.1	ENSP00000318878.3		O95013

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1128

AN:

15428

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.0444

Gnomad AMR

AF:

0.0906

Gnomad ASJ

AF:

0.0293

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.0351

Gnomad FIN

AF:

0.0811

Gnomad MID

AF:

0.0227

Gnomad NFE

AF:

0.0312

Gnomad OTH

AF:

0.0619

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0472

AC:

17422

AN:

369406

Hom.:

341

Cov.:

AF XY:

0.0457

AC XY:

8833

AN XY:

193244

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.0771

Gnomad4 ASJ exome

AF:

0.0336

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.0353

Gnomad4 FIN exome

AF:

0.0501

Gnomad4 NFE exome

AF:

0.0332

Gnomad4 OTH exome

AF:

0.0454

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0734

AC:

1135

AN:

15462

Hom.:

Cov.:

AF XY:

0.0743

AC XY:

525

AN XY:

7062

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.0907

Gnomad4 ASJ

AF:

0.0293

Gnomad4 EAS

AF:

0.136

Gnomad4 SAS

AF:

0.0348

Gnomad4 FIN

AF:

0.0811

Gnomad4 NFE

AF:

0.0312

Gnomad4 OTH

AF:

0.0577

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.75

DANN

Benign

0.55

DEOGEN2

Benign

0.0056

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.52

M_CAP

Benign

0.00095

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.61

PrimateAI

Benign

0.31

PROVEAN

Benign

0.64

REVEL

Benign

0.013

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.060

MVP

0.030

ClinPred

0.024

GERP RS

-1.1

Varity_R

0.021

gMVP

0.054

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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