16-7499721-A-G

Position:

• chr16-7499721-A-G

Variant summary

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

The NM_018723.4(RBFOX1):​c.28-18426A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,896 control chromosomes in the GnomAD database, including 3,209 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 0.20 (3209 hom., cov: 31)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740

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]

RBFOX1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.28-18426A>G		intron_variant		ENST00000550418.6	NP_061193.2
RBFOX1	NM_145893.3	c.88-18426A>G		intron_variant		ENST00000355637.9	NP_665900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.28-18426A>G		intron_variant		1	NM_018723.4	ENSP00000450031.1
RBFOX1	ENST00000355637.9	c.88-18426A>G		intron_variant		1	NM_145893.3	ENSP00000347855.4

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30679 AN: 151780 Hom.: 3205 Cov.: 31

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.202 AC: 30711 AN: 151896 Hom.: 3209 Cov.: 31 AF XY: 0.204 AC XY: 15152 AN XY: 74242

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.322

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.200

Alfa AF: 0.167 Hom.: 1482

Bravo AF: 0.202

Asia WGS AF: 0.233 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1532921; hg19: chr16-7549723;