chr16-6191182-G-A

Variant names:

• chr16-6191182-G-A
• rs1946127
• NM_018723.4:c.-126-125813G>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.-126-125813G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 148,338 control chromosomes in the GnomAD database, including 24,921 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 0.57 (24921 hom., cov: 25)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 10 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=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.-126-125813G>A		intron_variant	Intron 1 of 15	ENST00000550418.6	NP_061193.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.-126-125813G>A		intron_variant	Intron 1 of 15	1	NM_018723.4	ENSP00000450031.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 84916 AN: 148244 Hom.: 24905 Cov.: 25

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.573 AC: 84968 AN: 148338 Hom.: 24921 Cov.: 25 AF XY: 0.580 AC XY: 41811 AN XY: 72086

African (AFR) AF: 0.423 AC: 16867 AN: 39860

American (AMR) AF: 0.635 AC: 9501 AN: 14956

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1735 AN: 3446

East Asian (EAS) AF: 0.648 AC: 3244 AN: 5006

South Asian (SAS) AF: 0.638 AC: 2960 AN: 4638

European-Finnish (FIN) AF: 0.675 AC: 6560 AN: 9718

Middle Eastern (MID) AF: 0.479 AC: 134 AN: 280

European-Non Finnish (NFE) AF: 0.625 AC: 42200 AN: 67484

Other (OTH) AF: 0.550 AC: 1128 AN: 2050

Alfa AF: 0.598 Hom.: 81338

Bravo AF: 0.556

Asia WGS AF: 0.613 AC: 2130 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.3
DANN	Benign	0.63
PhyloP100		0.29
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: rs1946127; hg19: chr16-6241183;