chr16-7709134-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_018723.4(RBFOX1):c.1071+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.024 in 1,610,716 control chromosomes in the GnomAD database, including 602 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 31 hom., cov: 31)

Exomes 𝑓: 0.025 ( 571 hom. )

Consequence

RBFOX1
NM_018723.4 splice_region, intron

Scores

Splicing: ADA: 0.0004631

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.33

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 16-7709134-G-A is Benign according to our data. Variant chr16-7709134-G-A is described in ClinVar as [Benign]. Clinvar id is 241954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-7709134-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0175 (2668/152208) while in subpopulation SAS AF= 0.0274 (132/4820). AF 95% confidence interval is 0.0238. There are 31 homozygotes in gnomad4. There are 1361 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2668 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4 link	c.1071+3G>A		splice_region_variant, intron_variant	Intron 15 of 15	ENST00000550418.6	NP_061193.2	Q9NWB1-1Q59HD3
RBFOX1	NM_145893.3 link	c.1187+3G>A		splice_region_variant, intron_variant	Intron 13 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.1071+3G>A		splice_region_variant, intron_variant	Intron 15 of 15	1	NM_018723.4	ENSP00000450031.1		Q9NWB1-1
RBFOX1	ENST00000355637.9 link	c.1187+3G>A		splice_region_variant, intron_variant	Intron 13 of 13	1	NM_145893.3	ENSP00000347855.4		Q9NWB1-5

Frequencies

GnomAD3 genomes

AF:

0.0176

AC:

2672

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00367

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00996

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0276

Gnomad FIN

AF:

0.0407

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0248

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0205

AC:

5135

AN:

250658

Hom.:

AF XY:

0.0225

AC XY:

3042

AN XY:

135446

show subpopulations

Gnomad AFR exome

AF:

0.00283

Gnomad AMR exome

AF:

0.00870

Gnomad ASJ exome

AF:

0.0171

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0288

Gnomad FIN exome

AF:

0.0382

Gnomad NFE exome

AF:

0.0246

Gnomad OTH exome

AF:

0.0203

GnomAD4 exome

AF:

0.0247

AC:

36017

AN:

1458508

Hom.:

571

Cov.:

AF XY:

0.0251

AC XY:

18198

AN XY:

725726

show subpopulations

Gnomad4 AFR exome

AF:

0.00377

Gnomad4 AMR exome

AF:

0.00892

Gnomad4 ASJ exome

AF:

0.0181

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0294

Gnomad4 FIN exome

AF:

0.0353

Gnomad4 NFE exome

AF:

0.0262

Gnomad4 OTH exome

AF:

0.0225

GnomAD4 genome

AF:

0.0175

AC:

2668

AN:

152208

Hom.:

Cov.:

AF XY:

0.0183

AC XY:

1361

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00366

Gnomad4 AMR

AF:

0.00994

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0274

Gnomad4 FIN

AF:

0.0407

Gnomad4 NFE

AF:

0.0248

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0214

Hom.:

Bravo

AF:

0.0149

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0262

EpiControl

AF:

0.0265

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 12, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

RBFOX1-related disorder

Benign:1

May 29, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Idiopathic generalized epilepsy

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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

-0.43

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00046

dbscSNV1_RF

Benign

0.014

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