Genetic Variant RBFOX1:c.931-5226T>C (chr16-7671548-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_018723.4(RBFOX1):c.931-5226T>C variant causes a intron change. The variant allele was found at a frequency of 0.000000688 in 1,453,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RBFOX1
NM_018723.4 intron

Scores

Splicing: ADA: 0.4366

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.73

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.18).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4 link	c.931-5226T>C		intron_variant	Intron 13 of 15	ENST00000550418.6	NP_061193.2
RBFOX1	NM_145893.3 link	c.951-9T>C		intron_variant	Intron 9 of 13	ENST00000355637.9	NP_665900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6 link	c.931-5226T>C		intron_variant	Intron 13 of 15	1	NM_018723.4	ENSP00000450031.1
RBFOX1	ENST00000355637.9 link	c.951-9T>C		intron_variant	Intron 9 of 13	1	NM_145893.3	ENSP00000347855.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

249906

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453488

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723678

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33290

American (AMR)

AF:

0.00

AC:

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26084

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.00

AC:

AN:

85796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105092

Other (OTH)

AF:

0.00

AC:

AN:

60156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

3.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.44

dbscSNV1_RF

Benign

0.49

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over