rs8054147

chr16-6111221-C-T

Variant summary

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

The NM_018723.4(RBFOX1):c.-127+91229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 152,088 control chromosomes in the GnomAD database, including 35,586 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 (35586 hom., cov: 32)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_018723.4	c.-127+91229C>T		intron_variant		ENST00000550418.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-127+91229C>T		intron_variant		1	NM_018723.4	A1

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101676 AN: 151970 Hom.: 35514 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.669 AC: 101813 AN: 152088 Hom.: 35586 Cov.: 32 AF XY: 0.666 AC XY: 49489 AN XY: 74338

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.674

Alfa AF: 0.655 Hom.: 4841

Bravo AF: 0.690

Asia WGS AF: 0.695 AC: 2417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.56
Dann	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8054147; hg19: chr16-6161222;