rs7195574

chr16-6713299-A-Gchr16-6713299-A-T

Variant summary

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

The NM_018723.4(RBFOX1):c.-16+58649A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0963 in 151,950 control chromosomes in the GnomAD database, including 1,154 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 0.096 (1154 hom., cov: 31)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_018723.4	c.-16+58649A>G		intron_variant		ENST00000550418.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-16+58649A>G		intron_variant		1	NM_018723.4	A1

Frequencies

GnomAD3 genomes AF: 0.0961 AC: 14597 AN: 151832 Hom.: 1150 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0498

Gnomad ASJ AF: 0.0426

Gnomad EAS AF: 0.0525

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0782

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

GnomAD4 genome AF: 0.0963 AC: 14629 AN: 151950 Hom.: 1154 Cov.: 31 AF XY: 0.0935 AC XY: 6944 AN XY: 74258

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0498

Gnomad4 ASJ AF: 0.0426

Gnomad4 EAS AF: 0.0530

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.0550

Gnomad4 NFE AF: 0.0527

Gnomad4 OTH AF: 0.0774

Alfa AF: 0.0628 Hom.: 472

Bravo AF: 0.101

Asia WGS AF: 0.0380 AC: 135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.71
Dann	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7195574; hg19: chr16-6763300;