rs200320825

chr16-6316983-TTTC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018723.4(RBFOX1):c.-126-6_-126-4del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,534,148 control chromosomes in the GnomAD database, including 571 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (63 hom., cov: 32)
  • Exomes 𝑓: 0.023 (508 hom.)
• Consequence: RBFOX1 NM_018723.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.329

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 -10 ACMG points.

• BP6: Variant 16-6316983-TTTC-T is Benign according to our data. Variant chr16-6316983-TTTC-T is described in ClinVar as [Benign]. Clinvar id is 585480.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBFOX1	NM_018723.4	c.-126-6_-126-4del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000550418.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-126-6_-126-4del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018723.4	A1

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2906 AN: 152192 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.00632

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0320

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.00791

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0359

GnomAD3 exomes AF: 0.0227 AC: 3079 AN: 135766 Hom.: 79 AF XY: 0.0229 AC XY: 1685 AN XY: 73712

Gnomad AFR exome AF: 0.00561

Gnomad AMR exome AF: 0.0204

Gnomad ASJ exome AF: 0.0648

Gnomad EAS exome AF: 0.000286

Gnomad SAS exome AF: 0.0179

Gnomad FIN exome AF: 0.00932

Gnomad NFE exome AF: 0.0259

Gnomad OTH exome AF: 0.0364

GnomAD4 exome AF: 0.0230 AC: 31792 AN: 1381838 Hom.: 508 AF XY: 0.0234 AC XY: 15956 AN XY: 681952

Gnomad4 AFR exome AF: 0.00838

Gnomad4 AMR exome AF: 0.0220

Gnomad4 ASJ exome AF: 0.0679

Gnomad4 EAS exome AF: 0.0000840

Gnomad4 SAS exome AF: 0.0168

Gnomad4 FIN exome AF: 0.00924

Gnomad4 NFE exome AF: 0.0234

Gnomad4 OTH exome AF: 0.0297

GnomAD4 genome AF: 0.0190 AC: 2898 AN: 152310 Hom.: 63 Cov.: 32 AF XY: 0.0185 AC XY: 1378 AN XY: 74490

Gnomad4 AFR AF: 0.00625

Gnomad4 AMR AF: 0.0320

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0147

Gnomad4 FIN AF: 0.00791

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0272 Hom.: 23

Bravo AF: 0.0207

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 30, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200320825; hg19: chr16-6366984;