rs17139085

Positions:

• chr16-6000072-G-A

Variant summary

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

The NM_001415887.1(RBFOX1):​c.471+132737G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 151,880 control chromosomes in the GnomAD database, including 416 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 0.065 (416 hom., cov: 30)
• Consequence: RBFOX1 NM_001415887.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_001415887.1	c.471+132737G>A		intron_variant			NP_001402816.1
RBFOX1	NM_001415888.1	c.471+132737G>A		intron_variant			NP_001402817.1
RBFOX1	XM_017023318.3	c.471+132737G>A		intron_variant			XP_016878807.1
RBFOX1	XM_024450303.2	c.432+132737G>A		intron_variant			XP_024306071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000641259.1	c.351+132737G>A		intron_variant				ENSP00000493041.1
RBFOX1	ENST00000569895.3	n.436+132737G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9819 AN: 151764 Hom.: 417 Cov.: 30

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0924

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0685

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

GnomAD4 genome AF: 0.0646 AC: 9816 AN: 151880 Hom.: 416 Cov.: 30 AF XY: 0.0662 AC XY: 4910 AN XY: 74222

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.0928

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0827

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.0715

Gnomad4 NFE AF: 0.0776

Gnomad4 OTH AF: 0.0678

Alfa AF: 0.0805 Hom.: 282

Bravo AF: 0.0631

Asia WGS AF: 0.0890 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17139085; hg19: chr16-6050073;