NM_018723.4:c.28-139725C>G

Variant names:

• chr16-7378422-C-G
• rs7190881
• NM_018723.4:c.28-139725C>G

Variant summary

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

The NM_018723.4(RBFOX1):​c.28-139725C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,918 control chromosomes in the GnomAD database, including 28,130 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 0.60 (28130 hom., cov: 31)
• Consequence: RBFOX1 NM_018723.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018723.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	NM_018723.4	MANE Select	c.28-139725C>G		intron	N/A	NP_061193.2
	RBFOX1	NM_145893.3	MANE Plus Clinical	c.87+45334C>G		intron	N/A	NP_665900.1
	RBFOX1	NM_001415887.1		c.625-139725C>G		intron	N/A	NP_001402816.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000550418.6	TSL:1 MANE Select	c.28-139725C>G		intron	N/A	ENSP00000450031.1
	RBFOX1	ENST00000355637.9	TSL:1 MANE Plus Clinical	c.87+45334C>G		intron	N/A	ENSP00000347855.4
	RBFOX1	ENST00000311745.9	TSL:1	c.87+45334C>G		intron	N/A	ENSP00000309117.5

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91038 AN: 151800 Hom.: 28095 Cov.: 31

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.600 AC: 91123 AN: 151918 Hom.: 28130 Cov.: 31 AF XY: 0.601 AC XY: 44622 AN XY: 74224

African (AFR) AF: 0.743 AC: 30806 AN: 41450

American (AMR) AF: 0.537 AC: 8205 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2067 AN: 3468

East Asian (EAS) AF: 0.627 AC: 3208 AN: 5116

South Asian (SAS) AF: 0.627 AC: 3021 AN: 4816

European-Finnish (FIN) AF: 0.566 AC: 5965 AN: 10538

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.531 AC: 36070 AN: 67944

Other (OTH) AF: 0.551 AC: 1160 AN: 2106

Alfa AF: 0.425 Hom.: 1119

Bravo AF: 0.598

Asia WGS AF: 0.674 AC: 2341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0080
DANN	Benign	0.098
PhyloP100		-2.6
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: rs7190881; hg19: chr16-7428423;