rs8052357

Variant names:

• chr16-6118101-G-A
• rs8052357
• NM_018723.4:c.-127+98109G>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+98109G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,140 control chromosomes in the GnomAD database, including 35,343 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 (35343 hom., cov: 33)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-127+98109G>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+98109G>A		intron_variant	Intron 1 of 15	1	NM_018723.4	ENSP00000450031.1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101370 AN: 152022 Hom.: 35269 Cov.: 33

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.667 AC: 101510 AN: 152140 Hom.: 35343 Cov.: 33 AF XY: 0.664 AC XY: 49403 AN XY: 74354

African (AFR) AF: 0.874 AC: 36331 AN: 41560

American (AMR) AF: 0.656 AC: 10042 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2053 AN: 3472

East Asian (EAS) AF: 0.517 AC: 2670 AN: 5160

South Asian (SAS) AF: 0.703 AC: 3395 AN: 4828

European-Finnish (FIN) AF: 0.525 AC: 5538 AN: 10544

Middle Eastern (MID) AF: 0.707 AC: 205 AN: 290

European-Non Finnish (NFE) AF: 0.578 AC: 39289 AN: 67972

Other (OTH) AF: 0.671 AC: 1414 AN: 2108

Alfa AF: 0.605 Hom.: 14150

Bravo AF: 0.684

Asia WGS AF: 0.695 AC: 2414 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.91
DANN	Benign	0.54
PhyloP100		0.088
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: rs8052357; hg19: chr16-6168102;