rs761205127

Variant names:

• chr16-7518352-C-G
• rs761205127
• NM_018723.4:c.233C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-7518352-C-G
• chr16-7518352-C-A
• chr16-7518352-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018723.4(RBFOX1):​c.233C>G​(p.Ala78Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A78S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBFOX1 NM_018723.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.05
• Publications: 8 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14658454).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	NM_018723.4	MANE Select	c.233C>G	p.Ala78Gly	missense	Exon 5 of 16	NP_061193.2
	RBFOX1	NM_145893.3	MANE Plus Clinical	c.293C>G	p.Ala98Gly	missense	Exon 2 of 14	NP_665900.1	Q9NWB1-5
	RBFOX1	NM_001415887.1		c.830C>G	p.Ala277Gly	missense	Exon 8 of 20	NP_001402816.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBFOX1	ENST00000550418.6	TSL:1 MANE Select	c.233C>G	p.Ala78Gly	missense	Exon 5 of 16	ENSP00000450031.1	Q9NWB1-1
	RBFOX1	ENST00000355637.9	TSL:1 MANE Plus Clinical	c.293C>G	p.Ala98Gly	missense	Exon 2 of 14	ENSP00000347855.4	Q9NWB1-5
	RBFOX1	ENST00000311745.9	TSL:1	c.293C>G	p.Ala98Gly	missense	Exon 2 of 13	ENSP00000309117.5	Q9NWB1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Idiopathic generalized epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.050
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.0
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.017
Sift	Benign	0.14	T
Sift4G	Benign	0.24	T
Polyphen		0.017	B
Vest4		0.36
MutPred		0.32		Gain of loop (P = 3e-04)
MVP		0.21
MPC		0.0060
ClinPred		0.49	T
GERP RS		4.3
Varity_R		0.19
gMVP		0.45

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: rs761205127; hg19: chr16-7568354;