16-6055212-A-G

Variant summary

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

The NM_018723.4(RBFOX1):​c.-127+35220A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,094 control chromosomes in the GnomAD database, including 1,786 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 0.15 ( 1786 hom., cov: 31)

Consequence

RBFOX1
NM_018723.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.319
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=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RBFOX1NM_018723.4 linkuse as main transcriptc.-127+35220A>G intron_variant ENST00000550418.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RBFOX1ENST00000550418.6 linkuse as main transcriptc.-127+35220A>G intron_variant 1 NM_018723.4 A1Q9NWB1-1

Frequencies

GnomAD3 genomes
AF:
0.148
AC:
22478
AN:
151974
Hom.:
1785
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.153
Gnomad AMI
AF:
0.0274
Gnomad AMR
AF:
0.183
Gnomad ASJ
AF:
0.161
Gnomad EAS
AF:
0.283
Gnomad SAS
AF:
0.137
Gnomad FIN
AF:
0.154
Gnomad MID
AF:
0.179
Gnomad NFE
AF:
0.127
Gnomad OTH
AF:
0.161
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.148
AC:
22510
AN:
152094
Hom.:
1786
Cov.:
31
AF XY:
0.151
AC XY:
11195
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.153
Gnomad4 AMR
AF:
0.183
Gnomad4 ASJ
AF:
0.161
Gnomad4 EAS
AF:
0.284
Gnomad4 SAS
AF:
0.136
Gnomad4 FIN
AF:
0.154
Gnomad4 NFE
AF:
0.127
Gnomad4 OTH
AF:
0.161
Alfa
AF:
0.129
Hom.:
1230
Bravo
AF:
0.151
Asia WGS
AF:
0.209
AC:
725
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.47
DANN
Benign
0.52

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: rs17139244; hg19: chr16-6105213; API