chr16-6044556-C-A

Variant names:

• chr16-6044556-C-A
• rs12926282
• NM_018723.4:c.-127+24564C>A

Variant summary

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

The NM_018723.4(RBFOX1):​c.-127+24564C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,556 control chromosomes in the GnomAD database, including 5,319 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 0.25 (5319 hom., cov: 32)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 2 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=-0.55).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-127+24564C>A		intron_variant	Intron 1 of 15	ENST00000550418.6	NP_061193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-127+24564C>A		intron_variant	Intron 1 of 15	1	NM_018723.4	ENSP00000450031.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37610 AN: 151480 Hom.: 5321 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.219

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.248 AC: 37600 AN: 151556 Hom.: 5319 Cov.: 32 AF XY: 0.246 AC XY: 18182 AN XY: 73968

African (AFR) AF: 0.109 AC: 4496 AN: 41310

American (AMR) AF: 0.279 AC: 4242 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 893 AN: 3466

East Asian (EAS) AF: 0.199 AC: 1020 AN: 5136

South Asian (SAS) AF: 0.290 AC: 1388 AN: 4784

European-Finnish (FIN) AF: 0.283 AC: 2951 AN: 10442

Middle Eastern (MID) AF: 0.224 AC: 64 AN: 286

European-Non Finnish (NFE) AF: 0.319 AC: 21649 AN: 67908

Other (OTH) AF: 0.250 AC: 526 AN: 2102

Alfa AF: 0.249 Hom.: 984

Bravo AF: 0.242

Asia WGS AF: 0.227 AC: 790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.42
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12926282; hg19: chr16-6094557;