16-6012552-T-C

Variant names:

• chr16-6012552-T-C
• rs1424125
• ENST00000641259.1:c.351+145217T>C

Variant summary

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

The ENST00000641259.1(RBFOX1):​c.351+145217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,124 control chromosomes in the GnomAD database, including 38,445 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 0.70 (38445 hom., cov: 33)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_001415887.1	c.471+145217T>C		intron_variant	Intron 4 of 19		NP_001402816.1
RBFOX1	NM_001415888.1	c.471+145217T>C		intron_variant	Intron 4 of 17		NP_001402817.1
RBFOX1	XM_017023318.3	c.471+145217T>C		intron_variant	Intron 4 of 19		XP_016878807.1
RBFOX1	XM_024450303.2	c.432+145217T>C		intron_variant	Intron 3 of 18		XP_024306071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000641259.1	c.351+145217T>C		intron_variant	Intron 4 of 19			ENSP00000493041.1
RBFOX1	ENST00000569895.3	n.436+145217T>C		intron_variant	Intron 4 of 6	3

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106491 AN: 152006 Hom.: 38397 Cov.: 33

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.701 AC: 106595 AN: 152124 Hom.: 38445 Cov.: 33 AF XY: 0.707 AC XY: 52568 AN XY: 74336

African (AFR) AF: 0.860 AC: 35703 AN: 41524

American (AMR) AF: 0.743 AC: 11369 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2164 AN: 3470

East Asian (EAS) AF: 0.865 AC: 4463 AN: 5158

South Asian (SAS) AF: 0.756 AC: 3649 AN: 4824

European-Finnish (FIN) AF: 0.639 AC: 6751 AN: 10572

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40337 AN: 67970

Other (OTH) AF: 0.699 AC: 1475 AN: 2110

Alfa AF: 0.626 Hom.: 34753

Bravo AF: 0.717

Asia WGS AF: 0.831 AC: 2890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.0
DANN	Benign	0.56
PhyloP100		-0.045

Splicing

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

Other links and lift over

dbSNP: rs1424125; hg19: chr16-6062553;