rs6500742

Positions:

• chr16-6059220-T-C

Variant summary

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

The NM_018723.4(RBFOX1):​c.-127+39228T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,992 control chromosomes in the GnomAD database, including 23,441 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 0.55 (23441 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915

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]

(HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-127+39228T>C		intron_variant		ENST00000550418.6	NP_061193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-127+39228T>C		intron_variant		1	NM_018723.4	ENSP00000450031	A1
	ENST00000549303.1	n.145T>C		non_coding_transcript_exon_variant	2/4	2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83114 AN: 151872 Hom.: 23439 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.550

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.547 AC: 83151 AN: 151990 Hom.: 23441 Cov.: 32 AF XY: 0.545 AC XY: 40470 AN XY: 74270

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.551

Alfa AF: 0.594 Hom.: 11191

Bravo AF: 0.544

Asia WGS AF: 0.546 AC: 1900 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	12
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6500742; hg19: chr16-6109221;