rs8052395

Positions:

• chr16-5590185-G-A
• chr16-5590185-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000641259.1(RBFOX1):​c.259-8717G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,062 control chromosomes in the GnomAD database, including 33,238 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 0.64 (33238 hom., cov: 32)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_001415887.1	c.379-8717G>A		intron_variant
RBFOX1	NM_001415888.1	c.379-8717G>A		intron_variant
RBFOX1	XM_017023318.3	c.379-8717G>A		intron_variant
RBFOX1	XM_024450303.2	c.340-8717G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000585867.2	c.259-8717G>A		intron_variant		2
RBFOX1	ENST00000641259.1	c.259-8717G>A		intron_variant
RBFOX1	ENST00000569895.3	n.344-8717G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96474 AN: 151944 Hom.: 33184 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.591

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.635 AC: 96584 AN: 152062 Hom.: 33238 Cov.: 32 AF XY: 0.641 AC XY: 47615 AN XY: 74314

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.971

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.595

Alfa AF: 0.493 Hom.: 5760

Bravo AF: 0.645

Asia WGS AF: 0.854 AC: 2966 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8052395; hg19: chr16-5640186;