16-6056259-T-C

Variant summary

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

The NM_018723.4(RBFOX1):​c.-127+36267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,954 control chromosomes in the GnomAD database, including 11,179 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 0.37 ( 11179 hom., cov: 32)

Consequence

RBFOX1
NM_018723.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.94
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=-0.92).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RBFOX1NM_018723.4 linkuse as main transcriptc.-127+36267T>C 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.-127+36267T>C intron_variant 1 NM_018723.4 ENSP00000450031.1 Q9NWB1-1

Frequencies

GnomAD3 genomes
AF:
0.375
AC:
56916
AN:
151836
Hom.:
11163
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.283
Gnomad AMI
AF:
0.268
Gnomad AMR
AF:
0.418
Gnomad ASJ
AF:
0.439
Gnomad EAS
AF:
0.611
Gnomad SAS
AF:
0.349
Gnomad FIN
AF:
0.438
Gnomad MID
AF:
0.427
Gnomad NFE
AF:
0.393
Gnomad OTH
AF:
0.392
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.375
AC:
56967
AN:
151954
Hom.:
11179
Cov.:
32
AF XY:
0.380
AC XY:
28239
AN XY:
74250
show subpopulations
Gnomad4 AFR
AF:
0.283
Gnomad4 AMR
AF:
0.418
Gnomad4 ASJ
AF:
0.439
Gnomad4 EAS
AF:
0.611
Gnomad4 SAS
AF:
0.350
Gnomad4 FIN
AF:
0.438
Gnomad4 NFE
AF:
0.393
Gnomad4 OTH
AF:
0.397
Alfa
AF:
0.377
Hom.:
3033
Bravo
AF:
0.372
Asia WGS
AF:
0.464
AC:
1615
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.10
DANN
Benign
0.33

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: rs17139246; hg19: chr16-6106260; API