rs11647425

Variant names:

• chr16-6231604-T-A
• rs11647425
• NM_018723.4:c.-126-85391T>A

Your query was ambiguous. Multiple possible variants found:

• chr16-6231604-T-A
• chr16-6231604-T-C

Variant summary

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

The NM_001415887.1(RBFOX1):​c.472-85391T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,068 control chromosomes in the GnomAD database, including 32,177 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 0.64 (32177 hom., cov: 32)
• Consequence: RBFOX1 NM_001415887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.807
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001415887.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	NM_018723.4	MANE Select	c.-126-85391T>A		intron	N/A	NP_061193.2
	RBFOX1	NM_001415887.1		c.472-85391T>A		intron	N/A	NP_001402816.1
	RBFOX1	NM_001415888.1		c.472-85391T>A		intron	N/A	NP_001402817.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000550418.6	TSL:1 MANE Select	c.-126-85391T>A		intron	N/A	ENSP00000450031.1
	RBFOX1	ENST00000553186.5	TSL:1	c.-126-85391T>A		intron	N/A	ENSP00000447753.1
	RBFOX1	ENST00000547605.5	TSL:1	c.-126-85391T>A		intron	N/A	ENSP00000450402.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97694 AN: 151950 Hom.: 32163 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.733

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.643 AC: 97748 AN: 152068 Hom.: 32177 Cov.: 32 AF XY: 0.649 AC XY: 48248 AN XY: 74348

African (AFR) AF: 0.500 AC: 20714 AN: 41438

American (AMR) AF: 0.730 AC: 11157 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2479 AN: 3472

East Asian (EAS) AF: 0.766 AC: 3956 AN: 5166

South Asian (SAS) AF: 0.672 AC: 3241 AN: 4822

European-Finnish (FIN) AF: 0.747 AC: 7917 AN: 10600

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45960 AN: 67976

Other (OTH) AF: 0.686 AC: 1444 AN: 2104

Alfa AF: 0.654 Hom.: 4168

Bravo AF: 0.635

Asia WGS AF: 0.731 AC: 2543 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	0.043
DANN	Benign	0.53
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11647425; hg19: chr16-6281605;