rs11649669

Positions:

• chr16-5303564-A-G
• chr16-5303564-A-T

Variant summary

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

The NM_001415887.1(RBFOX1):​c.339+63459A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,908 control chromosomes in the GnomAD database, including 30,761 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 0.63 (30761 hom., cov: 31)
• Consequence: RBFOX1 NM_001415887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_001415887.1	c.339+63459A>G		intron_variant			NP_001402816.1
RBFOX1	NM_001415888.1	c.339+63459A>G		intron_variant			NP_001402817.1
RBFOX1	XM_017023318.3	c.339+63459A>G		intron_variant			XP_016878807.1
RBFOX1	XM_024450303.2	c.339+63459A>G		intron_variant			XP_024306071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000641259.1	c.219+63459A>G		intron_variant				ENSP00000493041.1
RBFOX1	ENST00000585867.2	c.219+63459A>G		intron_variant		2		ENSP00000493140.1
RBFOX1	ENST00000569895.3	n.304+63459A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95500 AN: 151790 Hom.: 30749 Cov.: 31

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.629 AC: 95531 AN: 151908 Hom.: 30761 Cov.: 31 AF XY: 0.628 AC XY: 46610 AN XY: 74240

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.689

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.627

Alfa AF: 0.676 Hom.: 55784

Bravo AF: 0.632

Asia WGS AF: 0.659 AC: 2290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11649669; hg19: chr16-5353565;