ENST00000641259.1:c.319-106955T>C

Variant names:

• chr16-5760348-T-C
• rs3910449
• ENST00000641259.1:c.319-106955T>C

Variant summary

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

The ENST00000641259.1(RBFOX1):​c.319-106955T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,822 control chromosomes in the GnomAD database, including 25,835 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 0.55 (25835 hom., cov: 31)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• 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

ENSG00000305294 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	NM_001415887.1		c.439-106955T>C		intron	N/A	NP_001402816.1
	RBFOX1	NM_001415888.1		c.439-106955T>C		intron	N/A	NP_001402817.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000641259.1		c.319-106955T>C		intron	N/A	ENSP00000493041.1	A0A286YEU2
	RBFOX1	ENST00000569895.3	TSL:3	n.404-106955T>C		intron	N/A
	ENSG00000305294	ENST00000810159.1		n.61+1656T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82789 AN: 151704 Hom.: 25782 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.546 AC: 82898 AN: 151822 Hom.: 25835 Cov.: 31 AF XY: 0.545 AC XY: 40413 AN XY: 74188

African (AFR) AF: 0.858 AC: 35530 AN: 41410

American (AMR) AF: 0.538 AC: 8198 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3470

East Asian (EAS) AF: 0.625 AC: 3218 AN: 5152

South Asian (SAS) AF: 0.531 AC: 2556 AN: 4818

European-Finnish (FIN) AF: 0.335 AC: 3522 AN: 10516

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26937 AN: 67908

Other (OTH) AF: 0.535 AC: 1126 AN: 2104

Alfa AF: 0.452 Hom.: 21384

Bravo AF: 0.573

Asia WGS AF: 0.607 AC: 2111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.49
PhyloP100		-0.34

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3910449;

hg19: chr16-5810349;