16-6078399-G-T

Position:

• chr16-6078399-G-T

Variant summary

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

The NM_018723.4(RBFOX1):​c.-127+58407G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 151,730 control chromosomes in the GnomAD database, including 53,753 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 0.84 (53753 hom., cov: 30)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_018723.4	c.-127+58407G>T		intron_variant		ENST00000550418.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-127+58407G>T		intron_variant		1	NM_018723.4	A1
	ENST00000549303.1	n.179-11675G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.837 AC: 126945 AN: 151616 Hom.: 53696 Cov.: 30

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.837 AC: 127054 AN: 151730 Hom.: 53753 Cov.: 30 AF XY: 0.829 AC XY: 61457 AN XY: 74110

Gnomad4 AFR AF: 0.959

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.723

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.812

Gnomad4 OTH AF: 0.818

Alfa AF: 0.787 Hom.: 3308

Bravo AF: 0.856

Asia WGS AF: 0.676 AC: 2353 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.13

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4124065; hg19: chr16-6128400;