rs11641750

chr16-6304935-G-Achr16-6304935-G-Cchr16-6304935-G-T

Variant summary

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

The NM_018723.4(RBFOX1):c.-126-12060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 146,642 control chromosomes in the GnomAD database, including 23,510 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 0.53 (23510 hom., cov: 28)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_018723.4	c.-126-12060G>A		intron_variant		ENST00000550418.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-126-12060G>A		intron_variant		1	NM_018723.4	A1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 77412 AN: 146556 Hom.: 23503 Cov.: 28

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.654

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.528 AC: 77432 AN: 146642 Hom.: 23510 Cov.: 28 AF XY: 0.533 AC XY: 38054 AN XY: 71368

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.558

Alfa AF: 0.628 Hom.: 31369

Bravo AF: 0.488

Asia WGS AF: 0.566 AC: 1967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.19
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11641750; hg19: chr16-6354936; COSMIC: COSV70566985;