Variant 16-5598961-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001415887.1(RBFOX1):c.438C>T(p.Ser146Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000446 in 1,530,450 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 1 hom. )

Consequence

RBFOX1
NM_001415887.1 splice_region, synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.81

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 16-5598961-C-T is Benign according to our data. Variant chr16-5598961-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388339.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.81 with no splicing effect.

BS2

High AC in GnomAd4 at 80 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
RBFOX1	NM_001415887.1 linkuse as main transcript	c.438C>T	p.Ser146Ser	splice_region_variant, synonymous_variant	3/20	NP_001402816.1
RBFOX1	NM_001415888.1 linkuse as main transcript	c.438C>T	p.Ser146Ser	splice_region_variant, synonymous_variant	3/18	NP_001402817.1
RBFOX1	XM_017023318.3 linkuse as main transcript	c.438C>T	p.Ser146Ser	splice_region_variant, synonymous_variant	3/20	XP_016878807.1
RBFOX1	XM_024450303.2 linkuse as main transcript	c.399C>T	p.Ser133Ser	splice_region_variant, synonymous_variant	2/19	XP_024306071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
RBFOX1	ENST00000641259.1 linkuse as main transcript	c.318C>T	p.Ser106Ser	splice_region_variant, synonymous_variant	3/20		ENSP00000493041.1	A0A286YEU2
RBFOX1	ENST00000585867.2 linkuse as main transcript	c.318C>T	p.Ser106Ser	synonymous_variant	3/3	2	ENSP00000493140.1	A0A286YFF2
RBFOX1	ENST00000569895.3 linkuse as main transcript	n.403C>T		splice_region_variant, non_coding_transcript_exon_variant	3/7	3
LINC01570	ENST00000662976.1 linkuse as main transcript	n.943-527G>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00104

AC:

140

AN:

134556

Hom.:

AF XY:

0.000983

AC XY:

AN XY:

73268

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000245

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000454

Gnomad OTH exome

AF:

0.000966

GnomAD4 exome

AF:

0.000438

AC:

603

AN:

1378186

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

320

AN XY:

680484

show subpopulations

Gnomad4 AFR exome

AF:

0.0000637

Gnomad4 AMR exome

AF:

0.000252

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000590

Gnomad4 NFE exome

AF:

0.000210

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000525

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.000555

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

RBFOX1: BP4, BP7, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.11

DANN

Benign

0.85

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