chr16-7404495-G-A

Variant names:

• chr16-7404495-G-A
• rs7186570
• NM_018723.4:c.28-113652G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018723.4(RBFOX1):​c.28-113652G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,058 control chromosomes in the GnomAD database, including 46,240 homozygotes. 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: 𝑓 0.78 (46240 hom., cov: 33)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• Publications: 7 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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.28-113652G>A		intron_variant	Intron 4 of 15	ENST00000550418.6	NP_061193.2
RBFOX1	NM_145893.3	c.87+71407G>A		intron_variant	Intron 1 of 13	ENST00000355637.9	NP_665900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.28-113652G>A		intron_variant	Intron 4 of 15	1	NM_018723.4	ENSP00000450031.1
RBFOX1	ENST00000355637.9	c.87+71407G>A		intron_variant	Intron 1 of 13	1	NM_145893.3	ENSP00000347855.4

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117942 AN: 151940 Hom.: 46228 Cov.: 33

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.778

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.776 AC: 118000 AN: 152058 Hom.: 46240 Cov.: 33 AF XY: 0.774 AC XY: 57471 AN XY: 74282

African (AFR) AF: 0.657 AC: 27243 AN: 41444

American (AMR) AF: 0.822 AC: 12562 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2777 AN: 3470

East Asian (EAS) AF: 0.753 AC: 3880 AN: 5152

South Asian (SAS) AF: 0.829 AC: 3996 AN: 4822

European-Finnish (FIN) AF: 0.797 AC: 8427 AN: 10574

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56574 AN: 68012

Other (OTH) AF: 0.779 AC: 1640 AN: 2104

Alfa AF: 0.811 Hom.: 170408

Bravo AF: 0.769

Asia WGS AF: 0.817 AC: 2839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.60
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7186570; hg19: chr16-7454496;