16-6001142-C-T

Variant names:

• chr16-6001142-C-T
• rs2059273
• ENST00000641259.1:c.351+133807C>T

Variant summary

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

The NM_001415887.1(RBFOX1):​c.471+133807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,192 control chromosomes in the GnomAD database, including 55,557 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 0.85 (55557 hom., cov: 32)
• Consequence: RBFOX1 NM_001415887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 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_001415887.1		c.471+133807C>T		intron	N/A	NP_001402816.1
	RBFOX1	NM_001415888.1		c.471+133807C>T		intron	N/A	NP_001402817.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000641259.1		c.351+133807C>T		intron	N/A	ENSP00000493041.1	A0A286YEU2
	RBFOX1	ENST00000569895.3	TSL:3	n.436+133807C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129263 AN: 152074 Hom.: 55504 Cov.: 32

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.850 AC: 129375 AN: 152192 Hom.: 55557 Cov.: 32 AF XY: 0.848 AC XY: 63056 AN XY: 74396

African (AFR) AF: 0.958 AC: 39812 AN: 41536

American (AMR) AF: 0.816 AC: 12485 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2812 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5148 AN: 5178

South Asian (SAS) AF: 0.925 AC: 4457 AN: 4818

European-Finnish (FIN) AF: 0.734 AC: 7766 AN: 10582

Middle Eastern (MID) AF: 0.840 AC: 247 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54075 AN: 67994

Other (OTH) AF: 0.848 AC: 1790 AN: 2112

Alfa AF: 0.830 Hom.: 46528

Bravo AF: 0.857

Asia WGS AF: 0.945 AC: 3286 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	0.56
DANN	Benign	0.25
PhyloP100		-0.57

Splicing

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

Other links and lift over

dbSNP: rs2059273; hg19: chr16-6051143;