rs145861898

Positions:

• chr16-7579788-C-G
• chr16-7579788-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018723.4(RBFOX1):​c.282C>G​(p.Asp94Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RBFOX1 NM_018723.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047094226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBFOX1	NM_018723.4	c.282C>G	p.Asp94Glu	missense_variant	6/16	ENST00000550418.6	NP_061193.2
RBFOX1	NM_145893.3	c.342C>G	p.Asp114Glu	missense_variant	3/14	ENST00000355637.9	NP_665900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBFOX1	ENST00000550418.6	c.282C>G	p.Asp94Glu	missense_variant	6/16	1	NM_018723.4	ENSP00000450031.1
RBFOX1	ENST00000355637.9	c.342C>G	p.Asp114Glu	missense_variant	3/14	1	NM_145893.3	ENSP00000347855.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250866 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135542

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461778 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.62
DEOGEN2	Benign	0.015	.;.;.;T;.;T;.;.;T;.;.;.;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.89	D;T;D;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.047	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.85	.;.;L;L;.;.;.;.;L;.;.;.;.;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.36	.;N;N;N;N;N;N;N;N;N;N;N;N;.;.
REVEL	Benign	0.18
Sift	Benign	0.69	.;T;T;T;T;T;T;T;T;T;T;T;T;.;.
Sift4G	Benign	1.0	.;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0080, 0.0050, 0.17, 0.99, 0.023, 0.58, 1.0	.;.;B;B;B;D;.;.;B;B;P;D;.;.;.
Vest4		0.36, 0.37, 0.40, 0.39, 0.38, 0.38, 0.37, 0.36, 0.37, 0.41
MutPred		0.18		.;.;.;.;Gain of glycosylation at T133 (P = 0.1912);Gain of glycosylation at T133 (P = 0.1912);.;.;.;.;.;.;.;.;.;
MVP		0.19
MPC		0.0045
ClinPred		0.17	T
GERP RS		-4.4
Varity_R		0.054
gMVP		0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs145861898; hg19: chr16-7629790;