dbSNP rs1555648980: RBFOX1:c.562-9T>C (chr16-7597362-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_018723.4(RBFOX1):c.562-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RBFOX1
NM_018723.4 intron

Scores

Splicing: ADA: 0.8937

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.54

Publications

0 publications found

Variant links:

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

RBFOX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 16-7597362-T-C is Benign according to our data. Variant chr16-7597362-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 460033.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4 link	c.562-9T>C		intron_variant	Intron 8 of 15	ENST00000550418.6	NP_061193.2	Q9NWB1-1Q59HD3
RBFOX1	NM_145893.3 link	c.622-9T>C		intron_variant	Intron 5 of 13	ENST00000355637.9	NP_665900.1	Q9NWB1-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6 link	c.562-9T>C		intron_variant	Intron 8 of 15	1	NM_018723.4	ENSP00000450031.1		Q9NWB1-1
RBFOX1	ENST00000355637.9 link	c.622-9T>C		intron_variant	Intron 5 of 13	1	NM_145893.3	ENSP00000347855.4		Q9NWB1-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1449436

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

721306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32972

American (AMR)

AF:

0.00

AC:

AN:

43078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25898

East Asian (EAS)

AF:

0.00

AC:

AN:

39278

South Asian (SAS)

AF:

0.00

AC:

AN:

84594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53220

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1104790

Other (OTH)

AF:

0.00

AC:

AN:

59878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Idiopathic generalized epilepsy

Benign:1

Jun 11, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

3.5

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.89

dbscSNV1_RF

Benign

0.47

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.25

Position offset: 9

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

Publications

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rs1555648980

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over