Variant 16-6483548-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001415889.1(RBFOX1):c.45+4C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,534,700 control chromosomes in the GnomAD database, including 253,723 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29558 hom., cov: 31)

Exomes 𝑓: 0.56 ( 224165 hom. )

Consequence

RBFOX1
NM_001415889.1 splice_region, intron

Scores

Splicing: ADA: 0.00003166

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.24

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:

RBFOX1 (HGNC:):

RBFOX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 16-6483548-C-A is Benign according to our data. Variant chr16-6483548-C-A is described in ClinVar as [Benign]. Clinvar id is 803210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 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.-64+166491C>A		intron_variant		ENST00000550418.6	NP_061193.2	Q9NWB1-1Q59HD3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6 linkuse as main transcript	c.-64+166491C>A		intron_variant		1	NM_018723.4	ENSP00000450031.1		Q9NWB1-1

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93296

AN:

151690

Hom.:

29522

Cov.:

show subpopulations

Gnomad AFR

AF:

0.757

Gnomad AMI

AF:

0.790

Gnomad AMR

AF:

0.539

Gnomad ASJ

AF:

0.616

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.429

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.587

Gnomad OTH

AF:

0.626

GnomAD3 exomes

AF:

0.518

AC:

66528

AN:

128324

Hom.:

18219

AF XY:

0.516

AC XY:

36277

AN XY:

70272

show subpopulations

Gnomad AFR exome

AF:

0.768

Gnomad AMR exome

AF:

0.424

Gnomad ASJ exome

AF:

0.605

Gnomad EAS exome

AF:

0.339

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.542

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.569

GnomAD4 exome

AF:

0.565

AC:

780718

AN:

1382896

Hom.:

224165

Cov.:

AF XY:

0.560

AC XY:

382358

AN XY:

682330

show subpopulations

Gnomad4 AFR exome

AF:

0.763

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.601

Gnomad4 EAS exome

AF:

0.313

Gnomad4 SAS exome

AF:

0.439

Gnomad4 FIN exome

AF:

0.553

Gnomad4 NFE exome

AF:

0.579

Gnomad4 OTH exome

AF:

0.569

GnomAD4 genome

AF:

0.615

AC:

93372

AN:

151804

Hom.:

29558

Cov.:

AF XY:

0.606

AC XY:

44958

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.757

Gnomad4 AMR

AF:

0.538

Gnomad4 ASJ

AF:

0.616

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.430

Gnomad4 FIN

AF:

0.544

Gnomad4 NFE

AF:

0.587

Gnomad4 OTH

AF:

0.625

Alfa

AF:

0.564

Hom.:

3893

Bravo

AF:

0.619

Asia WGS

AF:

0.429

AC:

1495

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Idiopathic generalized epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000032

dbscSNV1_RF

Benign

0.0080

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