chr16-6147834-G-A

Variant names:

• chr16-6147834-G-A
• rs12924838
• NM_018723.4:c.-127+127842G>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+127842G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,046 control chromosomes in the GnomAD database, including 13,251 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 0.39 (13251 hom., cov: 33)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	NM_018723.4	MANE Select	c.-127+127842G>A		intron	N/A	NP_061193.2
	RBFOX1	NM_001415887.1		c.472-169161G>A		intron	N/A	NP_001402816.1
	RBFOX1	NM_001415888.1		c.472-169161G>A		intron	N/A	NP_001402817.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000550418.6	TSL:1 MANE Select	c.-127+127842G>A		intron	N/A	ENSP00000450031.1
	RBFOX1	ENST00000553186.5	TSL:1	c.-127+127842G>A		intron	N/A	ENSP00000447753.1
	RBFOX1	ENST00000547605.5	TSL:1	c.-127+127842G>A		intron	N/A	ENSP00000450402.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59145 AN: 151926 Hom.: 13199 Cov.: 33

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.390 AC: 59257 AN: 152046 Hom.: 13251 Cov.: 33 AF XY: 0.391 AC XY: 29026 AN XY: 74310

African (AFR) AF: 0.615 AC: 25506 AN: 41474

American (AMR) AF: 0.429 AC: 6552 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1296 AN: 5142

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4820

European-Finnish (FIN) AF: 0.317 AC: 3346 AN: 10564

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.274 AC: 18623 AN: 67974

Other (OTH) AF: 0.394 AC: 832 AN: 2114

Alfa AF: 0.296 Hom.: 5546

Bravo AF: 0.407

Asia WGS AF: 0.316 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.069
DANN	Benign	0.25
PhyloP100		-1.1
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: rs12924838; hg19: chr16-6197835;