rs2342747

chr16-5818699-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000641259.1(RBFOX1):c.319-48604A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,152 control chromosomes in the GnomAD database, including 34,460 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 (34460 hom., cov: 33)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_001415887.1	c.439-48604A>G		intron_variant
RBFOX1	NM_001415888.1	c.439-48604A>G		intron_variant
RBFOX1	XM_017023318.3	c.439-48604A>G		intron_variant
RBFOX1	XM_024450303.2	c.400-48604A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000641259.1	c.319-48604A>G		intron_variant
RBFOX1	ENST00000569895.3	n.404-48604A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102126 AN: 152034 Hom.: 34440 Cov.: 33

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.672 AC: 102186 AN: 152152 Hom.: 34460 Cov.: 33 AF XY: 0.672 AC XY: 49994 AN XY: 74374

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.663

Alfa AF: 0.685 Hom.: 56891

Bravo AF: 0.660

Asia WGS AF: 0.726 AC: 2523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	2.8
Dann	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2342747; hg19: chr16-5868700;