chr16-5647394-T-C

Position:

• chr16-5647394-T-C

Variant summary

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

The ENST00000641259.1(RBFOX1):​c.318+48433T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,090 control chromosomes in the GnomAD database, including 29,067 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 0.58 (29067 hom., cov: 32)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_001415887.1	c.438+48433T>C		intron_variant			NP_001402816.1
RBFOX1	NM_001415888.1	c.438+48433T>C		intron_variant			NP_001402817.1
RBFOX1	XM_017023318.3	c.438+48433T>C		intron_variant			XP_016878807.1
RBFOX1	XM_024450303.2	c.399+48433T>C		intron_variant			XP_024306071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000641259.1	c.318+48433T>C		intron_variant				ENSP00000493041
RBFOX1	ENST00000569895.3	n.403+48433T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88431 AN: 151970 Hom.: 29063 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.582 AC: 88452 AN: 152090 Hom.: 29067 Cov.: 32 AF XY: 0.576 AC XY: 42848 AN XY: 74364

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.638

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.612

Alfa AF: 0.687 Hom.: 18179

Bravo AF: 0.560

Asia WGS AF: 0.310 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.46
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12934235; hg19: chr16-5697395;