Variant rs200320825 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_018723.4(RBFOX1):c.-126-6_-126-4del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,534,148 control chromosomes in the GnomAD database, including 571 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 63 hom., cov: 32)

Exomes 𝑓: 0.023 ( 508 hom. )

Consequence

RBFOX1
NM_018723.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.329

Variant links:

Genes affected

RBFOX1 (HGNC:18222): (RNA binding fox-1 homolog 1) The Fox-1 family of RNA-binding proteins is evolutionarily conserved, and regulates tissue-specific alternative splicing in metazoa. Fox-1 recognizes a (U)GCAUG stretch in regulated exons or in flanking introns. The protein binds to the C-terminus of ataxin-2 and may contribute to the restricted pathology of spinocerebellar ataxia type 2 (SCA2). Ataxin-2 is the product of the SCA2 gene which causes familial neurodegenerative diseases. Fox-1 and ataxin-2 are both localized in the trans-Golgi network. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

RBFOX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 16-6316983-TTTC-T is Benign according to our data. Variant chr16-6316983-TTTC-T is described in ClinVar as [Benign]. Clinvar id is 585480.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_018723.4 linkuse as main transcript	c.-126-6_-126-4del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000550418.6	NP_061193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6 linkuse as main transcript	c.-126-6_-126-4del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018723.4	ENSP00000450031	A1	Q9NWB1-1

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2906

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00632

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0320

Gnomad ASJ

AF:

0.0712

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.00791

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0241

Gnomad OTH

AF:

0.0359

GnomAD3 exomes

AF:

0.0227

AC:

3079

AN:

135766

Hom.:

AF XY:

0.0229

AC XY:

1685

AN XY:

73712

show subpopulations

Gnomad AFR exome

AF:

0.00561

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.0648

Gnomad EAS exome

AF:

0.000286

Gnomad SAS exome

AF:

0.0179

Gnomad FIN exome

AF:

0.00932

Gnomad NFE exome

AF:

0.0259

Gnomad OTH exome

AF:

0.0364

GnomAD4 exome

AF:

0.0230

AC:

31792

AN:

1381838

Hom.:

508

AF XY:

0.0234

AC XY:

15956

AN XY:

681952

show subpopulations

Gnomad4 AFR exome

AF:

0.00838

Gnomad4 AMR exome

AF:

0.0220

Gnomad4 ASJ exome

AF:

0.0679

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.0168

Gnomad4 FIN exome

AF:

0.00924

Gnomad4 NFE exome

AF:

0.0234

Gnomad4 OTH exome

AF:

0.0297

GnomAD4 genome

AF:

0.0190

AC:

2898

AN:

152310

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1378

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00625

Gnomad4 AMR

AF:

0.0320

Gnomad4 ASJ

AF:

0.0712

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.00791

Gnomad4 NFE

AF:

0.0241

Gnomad4 OTH

AF:

0.0355

Alfa

AF:

0.0272

Hom.:

Bravo

AF:

0.0207

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 30, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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