rs11648981

Variant names:

• chr16-6814818-G-A
• rs11648981
• NM_018723.4:c.-16+160168G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-6814818-G-A
• chr16-6814818-G-C

Variant summary

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

The NM_018723.4(RBFOX1):​c.-16+160168G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,890 control chromosomes in the GnomAD database, including 23,233 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 0.55 (23233 hom., cov: 31)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-16+160168G>A		intron_variant	Intron 3 of 15	ENST00000550418.6	NP_061193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-16+160168G>A		intron_variant	Intron 3 of 15	1	NM_018723.4	ENSP00000450031.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82982 AN: 151772 Hom.: 23194 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.547 AC: 83062 AN: 151890 Hom.: 23233 Cov.: 31 AF XY: 0.544 AC XY: 40403 AN XY: 74238

African (AFR) AF: 0.637 AC: 26372 AN: 41394

American (AMR) AF: 0.535 AC: 8168 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3468

East Asian (EAS) AF: 0.301 AC: 1547 AN: 5142

South Asian (SAS) AF: 0.391 AC: 1879 AN: 4800

European-Finnish (FIN) AF: 0.551 AC: 5817 AN: 10562

Middle Eastern (MID) AF: 0.517 AC: 150 AN: 290

European-Non Finnish (NFE) AF: 0.524 AC: 35614 AN: 67946

Other (OTH) AF: 0.533 AC: 1125 AN: 2110

Alfa AF: 0.521 Hom.: 50417

Bravo AF: 0.548

Asia WGS AF: 0.377 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.13
DANN	Benign	0.31
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11648981; hg19: chr16-6864819;