rs3910449

Positions:

• chr16-5760348-T-C

Variant summary

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

The ENST00000641259.1(RBFOX1):​c.319-106955T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,822 control chromosomes in the GnomAD database, including 25,835 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 (25835 hom., cov: 31)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_001415887.1	c.439-106955T>C		intron_variant
RBFOX1	NM_001415888.1	c.439-106955T>C		intron_variant
RBFOX1	XM_017023318.3	c.439-106955T>C		intron_variant
RBFOX1	XM_024450303.2	c.400-106955T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000641259.1	c.319-106955T>C		intron_variant
RBFOX1	ENST00000569895.3	n.404-106955T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82789 AN: 151704 Hom.: 25782 Cov.: 31

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.546 AC: 82898 AN: 151822 Hom.: 25835 Cov.: 31 AF XY: 0.545 AC XY: 40413 AN XY: 74188

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.535

Alfa AF: 0.433 Hom.: 14696

Bravo AF: 0.573

Asia WGS AF: 0.607 AC: 2111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3910449; hg19: chr16-5810349;