rs12933048

Positions:

• chr16-5644377-A-G
• chr16-5644377-A-T

Variant summary

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

The ENST00000641259.1(RBFOX1):​c.318+45416A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,168 control chromosomes in the GnomAD database, including 52,844 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 0.78 (52844 hom., cov: 32)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_001415887.1	c.438+45416A>G		intron_variant			NP_001402816.1
RBFOX1	NM_001415888.1	c.438+45416A>G		intron_variant			NP_001402817.1
RBFOX1	XM_017023318.3	c.438+45416A>G		intron_variant			XP_016878807.1
RBFOX1	XM_024450303.2	c.399+45416A>G		intron_variant			XP_024306071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000641259.1	c.318+45416A>G		intron_variant				ENSP00000493041
RBFOX1	ENST00000569895.3	n.403+45416A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118406 AN: 152048 Hom.: 52836 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.944

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.865

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.778 AC: 118435 AN: 152168 Hom.: 52844 Cov.: 32 AF XY: 0.784 AC XY: 58328 AN XY: 74408

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.944

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.982

Gnomad4 FIN AF: 0.993

Gnomad4 NFE AF: 0.968

Gnomad4 OTH AF: 0.826

Alfa AF: 0.867 Hom.: 6131

Bravo AF: 0.749

Asia WGS AF: 0.942 AC: 3272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.039
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12933048; hg19: chr16-5694378;