16-5435507-T-G

Variant names:

• chr16-5435507-T-G
• rs471459
• ENST00000641259.1:c.220-31709T>G

Variant summary

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

The ENST00000641259.1(RBFOX1):​c.220-31709T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,098 control chromosomes in the GnomAD database, including 34,122 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 (34122 hom., cov: 32)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.758 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.340-31709T>G		intron	N/A	NP_001402816.1
	RBFOX1	NM_001415888.1		c.340-31709T>G		intron	N/A	NP_001402817.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000641259.1		c.220-31709T>G		intron	N/A	ENSP00000493041.1
	RBFOX1	ENST00000585867.2	TSL:2	c.220-31709T>G		intron	N/A	ENSP00000493140.1
	RBFOX1	ENST00000569895.3	TSL:3	n.305-31709T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101090 AN: 151980 Hom.: 34071 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.665 AC: 101197 AN: 152098 Hom.: 34122 Cov.: 32 AF XY: 0.668 AC XY: 49659 AN XY: 74340

African (AFR) AF: 0.765 AC: 31721 AN: 41478

American (AMR) AF: 0.693 AC: 10591 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1952 AN: 3466

East Asian (EAS) AF: 0.679 AC: 3509 AN: 5168

South Asian (SAS) AF: 0.585 AC: 2824 AN: 4824

European-Finnish (FIN) AF: 0.683 AC: 7224 AN: 10584

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41267 AN: 67966

Other (OTH) AF: 0.650 AC: 1374 AN: 2114

Alfa AF: 0.580 Hom.: 3691

Bravo AF: 0.673

Asia WGS AF: 0.650 AC: 2260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.33
PhyloP100		-0.068

Splicing

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

Other links and lift over

dbSNP: rs471459; hg19: chr16-5485508;