rs2342747

Variant names:

• chr16-5818699-A-G
• rs2342747
• ENST00000641259.1:c.319-48604A>G

Variant summary

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

The ENST00000641259.1(RBFOX1):​c.319-48604A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,152 control chromosomes in the GnomAD database, including 34,460 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 0.67 (34460 hom., cov: 33)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• Publications: 17 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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641259.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	NM_001415887.1		c.439-48604A>G		intron	N/A	NP_001402816.1
	RBFOX1	NM_001415888.1		c.439-48604A>G		intron	N/A	NP_001402817.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000641259.1		c.319-48604A>G		intron	N/A	ENSP00000493041.1
	RBFOX1	ENST00000569895.3	TSL:3	n.404-48604A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102126 AN: 152034 Hom.: 34440 Cov.: 33

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.672 AC: 102186 AN: 152152 Hom.: 34460 Cov.: 33 AF XY: 0.672 AC XY: 49994 AN XY: 74374

African (AFR) AF: 0.643 AC: 26704 AN: 41514

American (AMR) AF: 0.609 AC: 9317 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2230 AN: 3466

East Asian (EAS) AF: 0.694 AC: 3588 AN: 5170

South Asian (SAS) AF: 0.700 AC: 3372 AN: 4814

European-Finnish (FIN) AF: 0.723 AC: 7658 AN: 10588

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47209 AN: 67990

Other (OTH) AF: 0.663 AC: 1401 AN: 2112

Alfa AF: 0.685 Hom.: 137887

Bravo AF: 0.660

Asia WGS AF: 0.726 AC: 2523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.46
PhyloP100		0.24

Splicing

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

Other links and lift over

dbSNP: rs2342747; hg19: chr16-5868700;