Variant 17-79106690-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001350451.2(RBFOX3):c.321C>T(p.Pro107=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00154 in 1,489,880 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 26 hom. )

Consequence

RBFOX3
NM_001350451.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.48

Variant links:

Genes affected

RBFOX3 (HGNC:27097): (RNA binding fox-1 homolog 3) This gene encodes a member of the RNA-binding FOX protein family which is involved in the regulation of alternative splicing of pre-mRNA. The protein has an N-terminal proline-rich region, an RNA recognition motif (RRM) domain, and a C-terminal alanine-rich region. This gene produces the neuronal nuclei (NeuN) antigen that has been widely used as a marker for post-mitotic neurons. This gene has its highest expression in the central nervous system and plays a prominent role in neural tissue development and regulation of adult brain function. Mutations in this gene have been associated with numerous neurological disorders. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2017]

RBFOX3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 17-79106690-G-A is Benign according to our data. Variant chr17-79106690-G-A is described in ClinVar as [Benign]. Clinvar id is 238284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00288 (439/152284) while in subpopulation EAS AF= 0.0186 (96/5174). AF 95% confidence interval is 0.016. There are 5 homozygotes in gnomad4. There are 245 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 439 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX3	NM_001350451.2 linkuse as main transcript	c.321C>T	p.Pro107=	synonymous_variant	6/15	ENST00000693108.1	NP_001337380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX3	ENST00000693108.1 linkuse as main transcript	c.321C>T	p.Pro107=	synonymous_variant	6/15		NM_001350451.2	ENSP00000510395

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

439

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0178

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0185

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00380

AC:

361

AN:

95036

Hom.:

AF XY:

0.00335

AC XY:

173

AN XY:

51602

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0239

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0148

Gnomad SAS exome

AF:

0.000209

Gnomad FIN exome

AF:

0.00258

Gnomad NFE exome

AF:

0.000328

Gnomad OTH exome

AF:

0.00319

GnomAD4 exome

AF:

0.00139

AC:

1853

AN:

1337596

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

866

AN XY:

658904

show subpopulations

Gnomad4 AFR exome

AF:

0.000260

Gnomad4 AMR exome

AF:

0.0258

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0270

Gnomad4 SAS exome

AF:

0.000172

Gnomad4 FIN exome

AF:

0.00251

Gnomad4 NFE exome

AF:

0.000196

Gnomad4 OTH exome

AF:

0.00218

GnomAD4 genome

AF:

0.00288

AC:

439

AN:

152284

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

245

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.0178

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0186

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000687

Hom.:

Bravo

AF:

0.00405

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

RBFOX3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 13, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Idiopathic generalized epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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