chr16-6078399-G-T

Variant names:

• chr16-6078399-G-T
• rs4124065
• NM_018723.4:c.-127+58407G>T

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+58407G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 151,730 control chromosomes in the GnomAD database, including 53,753 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 0.84 (53753 hom., cov: 30)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999
• Publications: 6 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

ENSG00000257180 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-127+58407G>T		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+58407G>T		intron_variant	Intron 1 of 15	1	NM_018723.4	ENSP00000450031.1

Frequencies

GnomAD3 genomes AF: 0.837 AC: 126945 AN: 151616 Hom.: 53696 Cov.: 30

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.837 AC: 127054 AN: 151730 Hom.: 53753 Cov.: 30 AF XY: 0.829 AC XY: 61457 AN XY: 74110

African (AFR) AF: 0.959 AC: 39786 AN: 41476

American (AMR) AF: 0.833 AC: 12716 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2548 AN: 3456

East Asian (EAS) AF: 0.723 AC: 3729 AN: 5158

South Asian (SAS) AF: 0.627 AC: 3010 AN: 4798

European-Finnish (FIN) AF: 0.729 AC: 7648 AN: 10496

Middle Eastern (MID) AF: 0.779 AC: 226 AN: 290

European-Non Finnish (NFE) AF: 0.812 AC: 55046 AN: 67772

Other (OTH) AF: 0.818 AC: 1725 AN: 2108

Alfa AF: 0.787 Hom.: 3308

Bravo AF: 0.856

Asia WGS AF: 0.676 AC: 2353 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.13
PhyloP100		-1.0
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: rs4124065; hg19: chr16-6128400;