ENST00000641259.1:c.318C>T

Variant names:

• chr16-5598961-C-T
• rs546602910
• ENST00000641259.1:c.318C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The ENST00000641259.1(RBFOX1):​c.318C>T​(p.Ser106Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000446 in 1,530,450 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (1 hom.)
• Consequence: RBFOX1 ENST00000641259.1 splice_region, synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.81
• 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]

ENSG00000301629 (HGNC:):

LINC01570 (HGNC:51382): (long intergenic non-protein coding RNA 1570)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 16-5598961-C-T is Benign according to our data. Variant chr16-5598961-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3388339.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.81 with no splicing effect.
• BS2: High AC in GnomAd4 at 80 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000641259.1. 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_001415887.1		c.438C>T	p.Ser146Ser	splice_region synonymous	Exon 3 of 20	NP_001402816.1
	RBFOX1	NM_001415888.1		c.438C>T	p.Ser146Ser	splice_region synonymous	Exon 3 of 18	NP_001402817.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000641259.1		c.318C>T	p.Ser106Ser	splice_region synonymous	Exon 3 of 20	ENSP00000493041.1	A0A286YEU2
	RBFOX1	ENST00000585867.2	TSL:2	c.318C>T	p.Ser106Ser	synonymous	Exon 3 of 3	ENSP00000493140.1	A0A286YFF2
	RBFOX1	ENST00000569895.3	TSL:3	n.403C>T		splice_region non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes AF: 0.000526 AC: 80 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00104 AC: 140 AN: 134556 AF XY: 0.000983

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000245

Gnomad ASJ exome AF: 0.0127

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.000454

Gnomad OTH exome AF: 0.000966

GnomAD4 exome AF: 0.000438 AC: 603 AN: 1378186 Hom.: 1 Cov.: 31 AF XY: 0.000470 AC XY: 320 AN XY: 680484

African (AFR) AF: 0.0000637 AC: 2 AN: 31382

American (AMR) AF: 0.000252 AC: 9 AN: 35684

Ashkenazi Jewish (ASJ) AF: 0.0119 AC: 300 AN: 25156

East Asian (EAS) AF: 0.00 AC: 0 AN: 35708

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79132

European-Finnish (FIN) AF: 0.0000590 AC: 2 AN: 33888

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5686

European-Non Finnish (NFE) AF: 0.000210 AC: 225 AN: 1073830

Other (OTH) AF: 0.00109 AC: 63 AN: 57720

GnomAD4 genome AF: 0.000525 AC: 80 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40 AN XY: 74446

African (AFR) AF: 0.0000241 AC: 1 AN: 41542

American (AMR) AF: 0.000392 AC: 6 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00184 Hom.: 0

Bravo AF: 0.000555

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.85
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs546602910; hg19: chr16-5648962;