rs1473145

Variant names:

• chr16-5708184-A-C
• rs1473145
• ENST00000641259.1:c.318+109223A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-5708184-A-C
• chr16-5708184-A-G
• chr16-5708184-A-T

Variant summary

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

The ENST00000641259.1(RBFOX1):​c.318+109223A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,196 control chromosomes in the GnomAD database, including 68,733 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 0.95 (68733 hom., cov: 31)
• Consequence: RBFOX1 ENST00000641259.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_001415887.1	c.438+109223A>C		intron_variant	Intron 3 of 19		NP_001402816.1
RBFOX1	NM_001415888.1	c.438+109223A>C		intron_variant	Intron 3 of 17		NP_001402817.1
RBFOX1	XM_017023318.3	c.438+109223A>C		intron_variant	Intron 3 of 19		XP_016878807.1
RBFOX1	XM_024450303.2	c.399+109223A>C		intron_variant	Intron 2 of 18		XP_024306071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000641259.1	c.318+109223A>C		intron_variant	Intron 3 of 19			ENSP00000493041.1
RBFOX1	ENST00000569895.3	n.403+109223A>C		intron_variant	Intron 3 of 6	3

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144497 AN: 152078 Hom.: 68674 Cov.: 31

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.940

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

GnomAD4 genome AF: 0.950 AC: 144614 AN: 152196 Hom.: 68733 Cov.: 31 AF XY: 0.951 AC XY: 70731 AN XY: 74400

African (AFR) AF: 0.943 AC: 39141 AN: 41520

American (AMR) AF: 0.944 AC: 14425 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3212 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5161 AN: 5162

South Asian (SAS) AF: 0.978 AC: 4706 AN: 4812

European-Finnish (FIN) AF: 0.973 AC: 10308 AN: 10594

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.948 AC: 64514 AN: 68036

Other (OTH) AF: 0.941 AC: 1989 AN: 2114

Alfa AF: 0.954 Hom.: 11000

Bravo AF: 0.948

Asia WGS AF: 0.979 AC: 3403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.35
PhyloP100		-0.58

Splicing

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

Other links and lift over

dbSNP: rs1473145; hg19: chr16-5758185;