chr16-6234148-C-G

Variant names:

• chr16-6234148-C-G
• rs933478
• NM_018723.4:c.-126-82847C>G

Variant summary

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

The NM_018723.4(RBFOX1):​c.-126-82847C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,968 control chromosomes in the GnomAD database, including 31,723 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 0.64 (31723 hom., cov: 31)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829
• Publications: 1 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-126-82847C>G		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.-126-82847C>G		intron_variant	Intron 1 of 15	1	NM_018723.4	ENSP00000450031.1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96905 AN: 151850 Hom.: 31710 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.638 AC: 96957 AN: 151968 Hom.: 31723 Cov.: 31 AF XY: 0.644 AC XY: 47809 AN XY: 74272

African (AFR) AF: 0.495 AC: 20519 AN: 41430

American (AMR) AF: 0.725 AC: 11078 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2421 AN: 3468

East Asian (EAS) AF: 0.770 AC: 3962 AN: 5146

South Asian (SAS) AF: 0.649 AC: 3125 AN: 4816

European-Finnish (FIN) AF: 0.744 AC: 7867 AN: 10570

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.672 AC: 45668 AN: 67950

Other (OTH) AF: 0.681 AC: 1436 AN: 2110

Alfa AF: 0.544 Hom.: 1636

Bravo AF: 0.631

Asia WGS AF: 0.729 AC: 2533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.42
PhyloP100		-0.83
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: rs933478; hg19: chr16-6284149;