rs12924838

Positions:

• chr16-6147834-G-A
• chr16-6147834-G-C

Variant summary

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

The NM_018723.4(RBFOX1):​c.-127+127842G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,046 control chromosomes in the GnomAD database, including 13,251 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 0.39 (13251 hom., cov: 33)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-127+127842G>A		intron_variant		ENST00000550418.6	NP_061193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-127+127842G>A		intron_variant		1	NM_018723.4	ENSP00000450031	A1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59145 AN: 151926 Hom.: 13199 Cov.: 33

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.390 AC: 59257 AN: 152046 Hom.: 13251 Cov.: 33 AF XY: 0.391 AC XY: 29026 AN XY: 74310

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.394

Alfa AF: 0.281 Hom.: 3544

Bravo AF: 0.407

Asia WGS AF: 0.316 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.069
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12924838; hg19: chr16-6197835;