rs748804086
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_018723.4(RBFOX1):c.220G>A(p.Glu74Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,436 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
RBFOX1
NM_018723.4 missense
NM_018723.4 missense
Scores
6
7
6
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 9.27
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RBFOX1 | ENST00000550418.6 | c.220G>A | p.Glu74Lys | missense_variant | Exon 5 of 16 | 1 | NM_018723.4 | ENSP00000450031.1 | ||
| RBFOX1 | ENST00000355637.9 | c.280G>A | p.Glu94Lys | missense_variant | Exon 2 of 14 | 1 | NM_145893.3 | ENSP00000347855.4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461436Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727020
GnomAD4 exome
AF:
AC:
3
AN:
1461436
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
727020
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;.;.;T;.;T;.;.;.;T;.;.;.;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;M;M;.;.;.;.;.;M;.;.;.;.;.;.
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
.;D;D;D;D;D;D;D;D;D;D;D;D;D;.;.
REVEL
Benign
Sift
Uncertain
.;D;D;D;D;D;D;D;D;D;D;D;D;D;.;.
Sift4G
Benign
.;T;T;T;D;T;D;T;T;T;T;T;T;T;T;T
Polyphen
0.99, 0.99, 1.0, 1.0, 0.97, 1.0
.;.;D;D;D;D;D;.;.;D;D;D;D;.;.;.
Vest4
0.74, 0.77, 0.81, 0.79, 0.84, 0.82, 0.75, 0.81, 0.78, 0.84, 0.81, 0.86
MutPred
0.26
.;.;.;.;Gain of methylation at E117 (P = 0.0026);Gain of methylation at E117 (P = 0.0026);.;.;.;.;.;.;.;.;.;.;
MVP
0.24
MPC
0.016
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at