rs10500355

Positions:

• chr16-7409346-T-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The ENST00000550418.6(RBFOX1):​c.28-108801T>A variant causes a intron change. The variant allele was found at a frequency of 0.292 in 152,150 control chromosomes in the GnomAD database, including 7,075 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 0.29 (7075 hom., cov: 33)
• Consequence: RBFOX1 ENST00000550418.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.76

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.13).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.28-108801T>A		intron_variant		ENST00000550418.6	NP_061193.2
RBFOX1	NM_145893.3	c.87+76258T>A		intron_variant		ENST00000355637.9	NP_665900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000355637.9	c.87+76258T>A		intron_variant		1	NM_145893.3	ENSP00000347855
RBFOX1	ENST00000550418.6	c.28-108801T>A		intron_variant		1	NM_018723.4	ENSP00000450031	A1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44355 AN: 152032 Hom.: 7076 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.0634

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.292 AC: 44389 AN: 152150 Hom.: 7075 Cov.: 33 AF XY: 0.285 AC XY: 21198 AN XY: 74372

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.0634

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.317

Alfa AF: 0.341 Hom.: 1267

Bravo AF: 0.288

Asia WGS AF: 0.159 AC: 553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.13
CADD	Benign	22
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10500355; hg19: chr16-7459347;