rs17760312

Variant names:

• chr16-7661986-G-C
• rs17760312
• NM_018723.4:c.891-2943G>C

Variant summary

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

The NM_018723.4(RBFOX1):​c.891-2943G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 151,742 control chromosomes in the GnomAD database, including 710 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 0.089 (710 hom., cov: 32)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.891-2943G>C		intron_variant	Intron 12 of 15	ENST00000550418.6	NP_061193.2
RBFOX1	NM_145893.3	c.950+8039G>C		intron_variant	Intron 9 of 13	ENST00000355637.9	NP_665900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.891-2943G>C		intron_variant	Intron 12 of 15	1	NM_018723.4	ENSP00000450031.1
RBFOX1	ENST00000355637.9	c.950+8039G>C		intron_variant	Intron 9 of 13	1	NM_145893.3	ENSP00000347855.4

Frequencies

GnomAD3 genomes AF: 0.0891 AC: 13514 AN: 151624 Hom.: 711 Cov.: 32

Gnomad AFR AF: 0.0359

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0933

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0934

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0890 AC: 13504 AN: 151742 Hom.: 710 Cov.: 32 AF XY: 0.0889 AC XY: 6590 AN XY: 74112

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.0932

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.0611

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.0934

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.104

Alfa AF: 0.102 Hom.: 110

Bravo AF: 0.0863

Asia WGS AF: 0.0790 AC: 273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.62

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: rs17760312; hg19: chr16-7711988;