chr16-6483548-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018723.4(RBFOX1):​c.-64+166491C>A variant causes a 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. 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_018723.4 intron

Scores

2
Splicing: ADA: 0.00003166
2

Clinical Significance

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

Conservation

PhyloP100: 2.24

Publications

6 publications found
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 Gene-Disease associations (from GenCC):
  • epilepsy
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • neurodevelopmental disorder
    Inheritance: AD Classification: LIMITED Submitted by: G2P
  • autism susceptibility 1
    Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
RBFOX1NM_018723.4 linkc.-64+166491C>A intron_variant Intron 2 of 15 ENST00000550418.6 NP_061193.2 Q9NWB1-1Q59HD3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBFOX1ENST00000550418.6 linkc.-64+166491C>A intron_variant Intron 2 of 15 1 NM_018723.4 ENSP00000450031.1 Q9NWB1-1

Frequencies

GnomAD3 genomes
AF:
0.615
AC:
93296
AN:
151690
Hom.:
29522
Cov.:
31
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
GnomAD2 exomes
AF:
0.518
AC:
66528
AN:
128324
AF XY:
0.516
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 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.:
52
AF XY:
0.560
AC XY:
382358
AN XY:
682330
show subpopulations
African (AFR)
AF:
0.763
AC:
24109
AN:
31586
American (AMR)
AF:
0.440
AC:
15709
AN:
35688
Ashkenazi Jewish (ASJ)
AF:
0.601
AC:
15142
AN:
25176
East Asian (EAS)
AF:
0.313
AC:
11177
AN:
35714
South Asian (SAS)
AF:
0.439
AC:
34810
AN:
79214
European-Finnish (FIN)
AF:
0.553
AC:
18461
AN:
33412
Middle Eastern (MID)
AF:
0.607
AC:
3455
AN:
5688
European-Non Finnish (NFE)
AF:
0.579
AC:
624918
AN:
1078550
Other (OTH)
AF:
0.569
AC:
32937
AN:
57868
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.468
Heterozygous variant carriers
0
18029
36057
54086
72114
90143
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
17320
34640
51960
69280
86600
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.615
AC:
93372
AN:
151804
Hom.:
29558
Cov.:
31
AF XY:
0.606
AC XY:
44958
AN XY:
74142
show subpopulations
African (AFR)
AF:
0.757
AC:
31367
AN:
41446
American (AMR)
AF:
0.538
AC:
8216
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
0.616
AC:
2138
AN:
3468
East Asian (EAS)
AF:
0.347
AC:
1767
AN:
5088
South Asian (SAS)
AF:
0.430
AC:
2062
AN:
4794
European-Finnish (FIN)
AF:
0.544
AC:
5715
AN:
10512
Middle Eastern (MID)
AF:
0.680
AC:
200
AN:
294
European-Non Finnish (NFE)
AF:
0.587
AC:
39874
AN:
67916
Other (OTH)
AF:
0.625
AC:
1319
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
1744
3489
5233
6978
8722
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
758
1516
2274
3032
3790
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.570
Hom.:
4109
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
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Idiopathic generalized epilepsy Benign:1
May 28, 2019
Mendelics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
16
DANN
Benign
0.74
PhyloP100
2.2
PromoterAI
0.041
Neutral
Mutation Taster
=96/4
polymorphism (auto)

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

Other links and lift over

dbSNP: rs7187508; hg19: chr16-6533549; API