16-7676827-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate
The ENST00000550418.6(RBFOX1):c.984C>T(p.Ala328Ala) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000685 in 1,460,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
RBFOX1
ENST00000550418.6 synonymous
ENST00000550418.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.26
Publications
1 publications found
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 Gene-Disease associations (from GenCC):
- epilepsyInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- neurodevelopmental disorderInheritance: AD Classification: LIMITED Submitted by: G2P
- autism susceptibility 1Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.17).
BP6
Variant 16-7676827-C-T is Benign according to our data. Variant chr16-7676827-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 529525.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000550418.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RBFOX1 | NM_018723.4 | MANE Select | c.984C>T | p.Ala328Ala | synonymous | Exon 14 of 16 | NP_061193.2 | ||
| RBFOX1 | NM_145893.3 | MANE Plus Clinical | c.1047C>T | p.Ala349Ala | synonymous | Exon 11 of 14 | NP_665900.1 | ||
| RBFOX1 | NM_001415887.1 | c.1581C>T | p.Ala527Ala | synonymous | Exon 17 of 20 | NP_001402816.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| RBFOX1 | ENST00000550418.6 | TSL:1 MANE Select | c.984C>T | p.Ala328Ala | synonymous | Exon 14 of 16 | ENSP00000450031.1 | ||
| RBFOX1 | ENST00000355637.9 | TSL:1 MANE Plus Clinical | c.1047C>T | p.Ala349Ala | synonymous | Exon 11 of 14 | ENSP00000347855.4 | ||
| RBFOX1 | ENST00000311745.9 | TSL:1 | c.1047C>T | p.Ala349Ala | synonymous | Exon 11 of 13 | ENSP00000309117.5 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251128 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251128
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460720Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726592 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1460720
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
726592
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33458
American (AMR)
AF:
AC:
0
AN:
44704
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26124
East Asian (EAS)
AF:
AC:
1
AN:
39664
South Asian (SAS)
AF:
AC:
0
AN:
86248
European-Finnish (FIN)
AF:
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
AC:
0
AN:
5746
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111026
Other (OTH)
AF:
AC:
0
AN:
60344
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Idiopathic generalized epilepsy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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