16-6082786-A-G

Position:

• chr16-6082786-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.-127+62794A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 152,214 control chromosomes in the GnomAD database, including 170 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 0.036 (170 hom., cov: 31)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-127+62794A>G		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+62794A>G		intron_variant		1	NM_018723.4	ENSP00000450031	A1
	ENST00000549303.1	n.179-7288A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5390 AN: 152096 Hom.: 163 Cov.: 31

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0491

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0244

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

GnomAD4 genome AF: 0.0356 AC: 5415 AN: 152214 Hom.: 170 Cov.: 31 AF XY: 0.0360 AC XY: 2681 AN XY: 74420

Gnomad4 AFR AF: 0.0662

Gnomad4 AMR AF: 0.0589

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0488

Gnomad4 SAS AF: 0.0162

Gnomad4 FIN AF: 0.0313

Gnomad4 NFE AF: 0.0149

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0159 Hom.: 6

Bravo AF: 0.0396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.86
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4786811; hg19: chr16-6132787;