rs6500744

Positions:

• chr16-6063660-C-T

Variant summary

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

The NM_018723.4(RBFOX1):​c.-127+43668C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,998 control chromosomes in the GnomAD database, including 15,359 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 0.45 (15359 hom., cov: 31)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-127+43668C>T		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+43668C>T		intron_variant		1	NM_018723.4	ENSP00000450031	A1
	ENST00000549303.1	n.178+4407C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68049 AN: 151880 Hom.: 15359 Cov.: 31

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.448 AC: 68077 AN: 151998 Hom.: 15359 Cov.: 31 AF XY: 0.444 AC XY: 32986 AN XY: 74278

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.452

Alfa AF: 0.460 Hom.: 12006

Bravo AF: 0.454

Asia WGS AF: 0.441 AC: 1535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6500744; hg19: chr16-6113661;