16-6084526-A-G

Variant names:

• chr16-6084526-A-G
• rs889699
• NM_018723.4:c.-127+64534A>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+64534A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,762 control chromosomes in the GnomAD database, including 19,108 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 0.50 (19108 hom., cov: 33)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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]

ENSG00000257180 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-127+64534A>G		intron_variant	Intron 1 of 15	ENST00000550418.6	NP_061193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-127+64534A>G		intron_variant	Intron 1 of 15	1	NM_018723.4	ENSP00000450031.1

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75523 AN: 151644 Hom.: 19109 Cov.: 33

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.498 AC: 75538 AN: 151762 Hom.: 19108 Cov.: 33 AF XY: 0.487 AC XY: 36135 AN XY: 74152

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.498

Alfa AF: 0.397 Hom.: 1082

Bravo AF: 0.503

Asia WGS AF: 0.351 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.82
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs889699; hg19: chr16-6134527;