rs11866781

Positions:

• chr16-7089172-T-C
• chr16-7089172-T-G

Variant summary

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

The NM_018723.4(RBFOX1):​c.27+37074T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,938 control chromosomes in the GnomAD database, including 22,564 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 0.53 (22564 hom., cov: 32)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_018723.4	c.27+37074T>C		intron_variant		ENST00000550418.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000550418.6	c.27+37074T>C		intron_variant		1	NM_018723.4	A1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80651 AN: 151820 Hom.: 22559 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.531 AC: 80692 AN: 151938 Hom.: 22564 Cov.: 32 AF XY: 0.540 AC XY: 40068 AN XY: 74244

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.610

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.559

Alfa AF: 0.574 Hom.: 33159

Bravo AF: 0.518

Asia WGS AF: 0.756 AC: 2625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11866781; hg19: chr16-7139173;