rs200320825

Variant names:

• chr16-6316983-TTTC-T
• rs200320825
• NM_018723.4:c.-126-6_-126-4delCTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018723.4(RBFOX1):​c.-126-6_-126-4delCTT variant causes a splice region, 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_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.329
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• autism susceptibility 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018723.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	NM_018723.4	MANE Select	c.-126-6_-126-4delCTT		splice_region intron	N/A	NP_061193.2
	RBFOX1	NM_001415887.1		c.472-6_472-4delCTT		splice_region intron	N/A	NP_001402816.1
	RBFOX1	NM_001415888.1		c.472-6_472-4delCTT		splice_region intron	N/A	NP_001402817.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000550418.6	TSL:1 MANE Select	c.-126-11_-126-9delTTC		intron	N/A	ENSP00000450031.1	Q9NWB1-1
	RBFOX1	ENST00000553186.5	TSL:1	c.-126-11_-126-9delTTC		intron	N/A	ENSP00000447753.1	Q9NWB1-3
	RBFOX1	ENST00000547605.5	TSL:1	c.-126-11_-126-9delTTC		intron	N/A	ENSP00000450402.1	F8VR27

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

GnomAD2 exomes AF: 0.0227 AC: 3079 AN: 135766 AF XY: 0.0229

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 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

African (AFR) AF: 0.00838 AC: 264 AN: 31516

American (AMR) AF: 0.0220 AC: 783 AN: 35630

Ashkenazi Jewish (ASJ) AF: 0.0679 AC: 1706 AN: 25132

East Asian (EAS) AF: 0.0000840 AC: 3 AN: 35718

South Asian (SAS) AF: 0.0168 AC: 1328 AN: 79062

European-Finnish (FIN) AF: 0.00924 AC: 313 AN: 33884

Middle Eastern (MID) AF: 0.0902 AC: 513 AN: 5688

European-Non Finnish (NFE) AF: 0.0234 AC: 25166 AN: 1077378

Other (OTH) AF: 0.0297 AC: 1716 AN: 57830

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

African (AFR) AF: 0.00625 AC: 260 AN: 41574

American (AMR) AF: 0.0320 AC: 489 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 247 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4830

European-Finnish (FIN) AF: 0.00791 AC: 84 AN: 10622

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0241 AC: 1637 AN: 68026

Other (OTH) AF: 0.0355 AC: 75 AN: 2114

Alfa AF: 0.0272 Hom.: 23

Bravo AF: 0.0207

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs200320825; hg19: chr16-6366984;