rs12447958

Variant names:

• chr16-6031911-A-G
• rs12447958
• NM_018723.4:c.-127+11919A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-6031911-A-G
• chr16-6031911-A-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+11919A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,182 control chromosomes in the GnomAD database, including 5,089 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 0.24 (5089 hom., cov: 32)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018723.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	NM_018723.4	MANE Select	c.-127+11919A>G		intron	N/A	NP_061193.2
	RBFOX1	NM_001415887.1		c.471+164576A>G		intron	N/A	NP_001402816.1
	RBFOX1	NM_001415888.1		c.471+164576A>G		intron	N/A	NP_001402817.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000550418.6	TSL:1 MANE Select	c.-127+11919A>G		intron	N/A	ENSP00000450031.1	Q9NWB1-1
	RBFOX1	ENST00000553186.5	TSL:1	c.-127+11919A>G		intron	N/A	ENSP00000447753.1	Q9NWB1-3
	RBFOX1	ENST00000547605.5	TSL:1	c.-127+11919A>G		intron	N/A	ENSP00000450402.1	F8VR27

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36878 AN: 152064 Hom.: 5091 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.242 AC: 36871 AN: 152182 Hom.: 5089 Cov.: 32 AF XY: 0.242 AC XY: 18005 AN XY: 74372

African (AFR) AF: 0.114 AC: 4729 AN: 41568

American (AMR) AF: 0.181 AC: 2765 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1161 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1368 AN: 5136

South Asian (SAS) AF: 0.282 AC: 1357 AN: 4820

European-Finnish (FIN) AF: 0.326 AC: 3456 AN: 10588

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21113 AN: 67986

Other (OTH) AF: 0.236 AC: 498 AN: 2112

Alfa AF: 0.284 Hom.: 11111

Bravo AF: 0.226

Asia WGS AF: 0.215 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0030
DANN	Benign	0.50
PhyloP100		-0.74
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: rs12447958; hg19: chr16-6081912;