rs9302801

Variant names:

• chr16-5273896-G-A
• rs9302801
• ENST00000641259.1:c.219+33791G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001415887.1(RBFOX1):​c.339+33791G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,954 control chromosomes in the GnomAD database, including 22,294 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 0.53 (22294 hom., cov: 31)
• Consequence: RBFOX1 NM_001415887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_001415887.1	c.339+33791G>A		intron_variant	Intron 1 of 19		NP_001402816.1
RBFOX1	NM_001415888.1	c.339+33791G>A		intron_variant	Intron 1 of 17		NP_001402817.1
RBFOX1	XM_017023318.3	c.339+33791G>A		intron_variant	Intron 1 of 19		XP_016878807.1
RBFOX1	XM_024450303.2	c.339+33791G>A		intron_variant	Intron 1 of 18		XP_024306071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000641259.1	c.219+33791G>A		intron_variant	Intron 1 of 19			ENSP00000493041.1
RBFOX1	ENST00000585867.2	c.219+33791G>A		intron_variant	Intron 1 of 2	2		ENSP00000493140.1
RBFOX1	ENST00000569895.3	n.304+33791G>A		intron_variant	Intron 1 of 6	3

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80616 AN: 151840 Hom.: 22272 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.531 AC: 80682 AN: 151954 Hom.: 22294 Cov.: 31 AF XY: 0.530 AC XY: 39322 AN XY: 74260

African (AFR) AF: 0.698 AC: 28928 AN: 41432

American (AMR) AF: 0.446 AC: 6817 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1581 AN: 3466

East Asian (EAS) AF: 0.321 AC: 1650 AN: 5146

South Asian (SAS) AF: 0.469 AC: 2258 AN: 4810

European-Finnish (FIN) AF: 0.527 AC: 5566 AN: 10568

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32195 AN: 67948

Other (OTH) AF: 0.495 AC: 1045 AN: 2110

Alfa AF: 0.521 Hom.: 2658

Bravo AF: 0.530

Asia WGS AF: 0.388 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.15
DANN	Benign	0.71
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs9302801; hg19: chr16-5323897;