16-7108553-T-C

Position:

• chr16-7108553-T-C

Variant summary

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

The NM_018723.4(RBFOX1):​c.27+56455T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,054 control chromosomes in the GnomAD database, including 8,581 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 0.32 (8581 hom., cov: 32)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.27+56455T>C		intron_variant		ENST00000550418.6	NP_061193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.27+56455T>C		intron_variant		1	NM_018723.4	ENSP00000450031.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48605 AN: 151938 Hom.: 8583 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.320 AC: 48621 AN: 152054 Hom.: 8581 Cov.: 32 AF XY: 0.320 AC XY: 23769 AN XY: 74336

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.329

Alfa AF: 0.367 Hom.: 13830

Bravo AF: 0.304

Asia WGS AF: 0.257 AC: 895 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.96
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1478697; hg19: chr16-7158554;