rs11648981

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018723.4(RBFOX1):​c.-16+160168G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,890 control chromosomes in the GnomAD database, including 23,233 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 23233 hom., cov: 31)

Consequence

RBFOX1
NM_018723.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.30
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RBFOX1NM_018723.4 linkuse as main transcriptc.-16+160168G>A intron_variant ENST00000550418.6 NP_061193.2 Q9NWB1-1Q59HD3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RBFOX1ENST00000550418.6 linkuse as main transcriptc.-16+160168G>A intron_variant 1 NM_018723.4 ENSP00000450031.1 Q9NWB1-1

Frequencies

GnomAD3 genomes
AF:
0.547
AC:
82982
AN:
151772
Hom.:
23194
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.637
Gnomad AMI
AF:
0.476
Gnomad AMR
AF:
0.535
Gnomad ASJ
AF:
0.565
Gnomad EAS
AF:
0.301
Gnomad SAS
AF:
0.393
Gnomad FIN
AF:
0.551
Gnomad MID
AF:
0.506
Gnomad NFE
AF:
0.524
Gnomad OTH
AF:
0.536
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.547
AC:
83062
AN:
151890
Hom.:
23233
Cov.:
31
AF XY:
0.544
AC XY:
40403
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.637
Gnomad4 AMR
AF:
0.535
Gnomad4 ASJ
AF:
0.565
Gnomad4 EAS
AF:
0.301
Gnomad4 SAS
AF:
0.391
Gnomad4 FIN
AF:
0.551
Gnomad4 NFE
AF:
0.524
Gnomad4 OTH
AF:
0.533
Alfa
AF:
0.516
Hom.:
32491
Bravo
AF:
0.548
Asia WGS
AF:
0.377
AC:
1314
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.13
DANN
Benign
0.31

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.

Other links and lift over

dbSNP: rs11648981; hg19: chr16-6864819; API