rs143695164

chr16-7518215-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_018723.4(RBFOX1):c.96C>G(p.Pro32=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000757 in 1,614,122 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (2 hom.)
• Consequence: RBFOX1 NM_018723.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0640

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 16-7518215-C-G is Benign according to our data. Variant chr16-7518215-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 415962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.064 with no splicing effect.
• BS2: High AC in GnomAd at 85 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_018723.4	c.96C>G	p.Pro32=	synonymous_variant	5/16	ENST00000550418.6
RBFOX1	NM_145893.3	c.156C>G	p.Pro52=	synonymous_variant	2/14	ENST00000355637.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000550418.6	c.96C>G	p.Pro32=	synonymous_variant	5/16	1	NM_018723.4	A1
RBFOX1	ENST00000355637.9	c.156C>G	p.Pro52=	synonymous_variant	2/14	1	NM_145893.3

Frequencies

GnomAD3 genomes AF: 0.000559 AC: 85 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000801 AC: 201 AN: 250882 Hom.: 1 AF XY: 0.000892 AC XY: 121 AN XY: 135578

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000608

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00239

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000786

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000778 AC: 1138 AN: 1461832 Hom.: 2 Cov.: 31 AF XY: 0.000835 AC XY: 607 AN XY: 727214

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.000803

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00285

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.000693

Gnomad4 OTH exome AF: 0.000795

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74468

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000848 Hom.: 0

Bravo AF: 0.000518

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000533

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Mar 12, 2018

- -

Idiopathic generalized epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	5.7
Dann	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs143695164; hg19: chr16-7568217;