chr16-6860384-A-T

Variant names:

• chr16-6860384-A-T
• rs12921846
• NM_018723.4:c.-15-191673A>T

Variant summary

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

The NM_018723.4(RBFOX1):​c.-15-191673A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,060 control chromosomes in the GnomAD database, including 7,153 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 0.28 (7153 hom., cov: 32)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-15-191673A>T		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.-15-191673A>T		intron_variant	Intron 3 of 15	1	NM_018723.4	ENSP00000450031.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41786 AN: 151942 Hom.: 7138 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.275 AC: 41827 AN: 152060 Hom.: 7153 Cov.: 32 AF XY: 0.274 AC XY: 20386 AN XY: 74320

African (AFR) AF: 0.473 AC: 19605 AN: 41458

American (AMR) AF: 0.192 AC: 2935 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3464

East Asian (EAS) AF: 0.333 AC: 1719 AN: 5164

South Asian (SAS) AF: 0.387 AC: 1862 AN: 4808

European-Finnish (FIN) AF: 0.146 AC: 1542 AN: 10572

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.187 AC: 12704 AN: 68010

Other (OTH) AF: 0.248 AC: 523 AN: 2112

Alfa AF: 0.183 Hom.: 1594

Bravo AF: 0.289

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.029
DANN	Benign	0.71
PhyloP100		-2.6
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: rs12921846; hg19: chr16-6910385;