NM_018723.4:c.96C>G

Variant names:

• chr16-7518215-C-G
• rs143695164
• NM_018723.4:c.96C>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_018723.4(RBFOX1):​c.96C>G​(p.Pro32Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000757 in 1,614,122 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (2 hom.)
• Consequence: RBFOX1 NM_018723.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0640
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 16-7518215-C-G is Benign according to our data. Variant chr16-7518215-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 415962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.064 with no splicing effect.
• BS2: High AC in GnomAd4 at 84 Unknown,AD gene.

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.96C>G	p.Pro32Pro	synonymous	Exon 5 of 16	NP_061193.2
	RBFOX1	NM_145893.3	MANE Plus Clinical	c.156C>G	p.Pro52Pro	synonymous	Exon 2 of 14	NP_665900.1	Q9NWB1-5
	RBFOX1	NM_001415887.1		c.693C>G	p.Pro231Pro	synonymous	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.96C>G	p.Pro32Pro	synonymous	Exon 5 of 16	ENSP00000450031.1	Q9NWB1-1
	RBFOX1	ENST00000355637.9	TSL:1 MANE Plus Clinical	c.156C>G	p.Pro52Pro	synonymous	Exon 2 of 14	ENSP00000347855.4	Q9NWB1-5
	RBFOX1	ENST00000311745.9	TSL:1	c.156C>G	p.Pro52Pro	synonymous	Exon 2 of 13	ENSP00000309117.5	Q9NWB1-2

Frequencies

GnomAD3 genomes AF: 0.000559 AC: 85 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000801 AC: 201 AN: 250882 AF XY: 0.000892

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000608

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000786

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000778 AC: 1138 AN: 1461832 Hom.: 2 Cov.: 31 AF XY: 0.000835 AC XY: 607 AN XY: 727214

African (AFR) AF: 0.000209 AC: 7 AN: 33478

American (AMR) AF: 0.000559 AC: 25 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.000803 AC: 21 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00285 AC: 246 AN: 86240

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53420

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.000693 AC: 771 AN: 1111984

Other (OTH) AF: 0.000795 AC: 48 AN: 60390

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74468

African (AFR) AF: 0.0000962 AC: 4 AN: 41582

American (AMR) AF: 0.000588 AC: 9 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68016

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000848 Hom.: 0

Bravo AF: 0.000518

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Idiopathic generalized epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	5.7
DANN	Benign	0.80
PhyloP100		0.064
Mutation Taster		=100/0	polymorphism

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: rs143695164; hg19: chr16-7568217;