rs3785214

chr16-7667119-A-Cchr16-7667119-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018723.4(RBFOX1):c.930+2151A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,016 control chromosomes in the GnomAD database, including 12,700 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 (12700 hom., cov: 32)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.650

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_018723.4	c.930+2151A>C		intron_variant		ENST00000550418.6
RBFOX1	NM_145893.3	c.951-4438A>C		intron_variant		ENST00000355637.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000355637.9	c.951-4438A>C		intron_variant		1	NM_145893.3
RBFOX1	ENST00000550418.6	c.930+2151A>C		intron_variant		1	NM_018723.4	A1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58755 AN: 151900 Hom.: 12701 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.387 AC: 58763 AN: 152016 Hom.: 12700 Cov.: 32 AF XY: 0.382 AC XY: 28353 AN XY: 74302

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.393

Alfa AF: 0.456 Hom.: 3348

Bravo AF: 0.387

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.9
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3785214; hg19: chr16-7717121; COSMIC: COSV60979283;