Variant 16-7579839-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000550418.6(RBFOX1):c.333A>G(p.Glu111=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,614,028 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 12 hom., cov: 32)

Exomes 𝑓: 0.012 ( 160 hom. )

Consequence

RBFOX1
ENST00000550418.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.79

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 16-7579839-A-G is Benign according to our data. Variant chr16-7579839-A-G is described in ClinVar as [Benign]. Clinvar id is 415961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.79 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00987 (1502/152228) while in subpopulation SAS AF= 0.0185 (89/4822). AF 95% confidence interval is 0.0154. There are 12 homozygotes in gnomad4. There are 739 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1502 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_018723.4 linkuse as main transcript	c.333A>G	p.Glu111=	synonymous_variant	6/16	ENST00000550418.6	NP_061193.2
RBFOX1	NM_145893.3 linkuse as main transcript	c.393A>G	p.Glu131=	synonymous_variant	3/14	ENST00000355637.9	NP_665900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6 linkuse as main transcript	c.333A>G	p.Glu111=	synonymous_variant	6/16	1	NM_018723.4	ENSP00000450031	A1	Q9NWB1-1
RBFOX1	ENST00000355637.9 linkuse as main transcript	c.393A>G	p.Glu131=	synonymous_variant	3/14	1	NM_145893.3	ENSP00000347855		Q9NWB1-5

Frequencies

GnomAD3 genomes

AF:

0.00989

AC:

1505

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00806

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0184

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.0131

AC:

3278

AN:

251056

Hom.:

AF XY:

0.0142

AC XY:

1924

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.0481

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0205

Gnomad FIN exome

AF:

0.0185

Gnomad NFE exome

AF:

0.0136

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0118

AC:

17254

AN:

1461800

Hom.:

160

Cov.:

AF XY:

0.0122

AC XY:

8879

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00420

Gnomad4 ASJ exome

AF:

0.0459

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0214

Gnomad4 FIN exome

AF:

0.0174

Gnomad4 NFE exome

AF:

0.0110

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.00987

AC:

1502

AN:

152228

Hom.:

Cov.:

AF XY:

0.00993

AC XY:

739

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00805

Gnomad4 ASJ

AF:

0.0438

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0185

Gnomad4 FIN

AF:

0.0172

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.0136

Hom.:

Bravo

AF:

0.00813

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Oct 05, 2017	- -

Idiopathic generalized epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.0

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over