rs8060283

Variant names:

• chr16-5731709-A-G
• rs8060283
• ENST00000641259.1:c.318+132748A>G

Variant summary

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

The ENST00000641259.1(RBFOX1):​c.318+132748A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,186 control chromosomes in the GnomAD database, including 7,473 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 0.18 (7473 hom., cov: 33)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_001415887.1	c.438+132748A>G		intron_variant	Intron 3 of 19		NP_001402816.1
RBFOX1	NM_001415888.1	c.438+132748A>G		intron_variant	Intron 3 of 17		NP_001402817.1
RBFOX1	XM_017023318.3	c.438+132748A>G		intron_variant	Intron 3 of 19		XP_016878807.1
RBFOX1	XM_024450303.2	c.399+132748A>G		intron_variant	Intron 2 of 18		XP_024306071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000641259.1	c.318+132748A>G		intron_variant	Intron 3 of 19			ENSP00000493041.1
RBFOX1	ENST00000569895.3	n.403+132748A>G		intron_variant	Intron 3 of 6	3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27625 AN: 152070 Hom.: 7454 Cov.: 33

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.00737

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.182 AC: 27689 AN: 152186 Hom.: 7473 Cov.: 33 AF XY: 0.180 AC XY: 13408 AN XY: 74418

African (AFR) AF: 0.589 AC: 24407 AN: 41456

American (AMR) AF: 0.0689 AC: 1055 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.147 AC: 762 AN: 5180

South Asian (SAS) AF: 0.110 AC: 532 AN: 4826

European-Finnish (FIN) AF: 0.0118 AC: 125 AN: 10614

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.00737 AC: 501 AN: 68016

Other (OTH) AF: 0.132 AC: 279 AN: 2110

Alfa AF: 0.0689 Hom.: 6964

Bravo AF: 0.203

Asia WGS AF: 0.136 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.1
DANN	Benign	0.50
PhyloP100		-0.0010

Splicing

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

Other links and lift over

dbSNP: rs8060283; hg19: chr16-5781710;