dbSNP rs990728601: RBFOX3:p.Ala341Ala (chr17-79094505-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001350451.2(RBFOX3):c.1023C>T(p.Ala341Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000597 in 1,456,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

RBFOX3
NM_001350451.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.115

Publications

0 publications found

Variant links:

Genes affected

RBFOX3 (HGNC:27097): (RNA binding fox-1 homolog 3) This gene encodes a member of the RNA-binding FOX protein family which is involved in the regulation of alternative splicing of pre-mRNA. The protein has an N-terminal proline-rich region, an RNA recognition motif (RRM) domain, and a C-terminal alanine-rich region. This gene produces the neuronal nuclei (NeuN) antigen that has been widely used as a marker for post-mitotic neurons. This gene has its highest expression in the central nervous system and plays a prominent role in neural tissue development and regulation of adult brain function. Mutations in this gene have been associated with numerous neurological disorders. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2017]

RBFOX3 Gene-Disease associations (from GenCC):

epilepsy
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Ambry Genetics

RBFOX3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 17-79094505-G-A is Benign according to our data. Variant chr17-79094505-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1114814.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.115 with no splicing effect.

BS2

High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350451.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBFOX3	NM_001350451.2	MANE Select	c.1023C>T	p.Ala341Ala	synonymous	Exon 14 of 15	NP_001337380.1	A0A8I5KWJ3
RBFOX3	NM_001385804.1		c.1023C>T	p.Ala341Ala	synonymous	Exon 14 of 15	NP_001372733.1
RBFOX3	NM_001385805.1		c.1023C>T	p.Ala341Ala	synonymous	Exon 15 of 16	NP_001372734.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBFOX3	ENST00000693108.1	MANE Select	c.1023C>T	p.Ala341Ala	synonymous	Exon 14 of 15	ENSP00000510395.1	A0A8I5KWJ3
RBFOX3	ENST00000857749.1		c.1119C>T	p.Ala373Ala	synonymous	Exon 14 of 15	ENSP00000527808.1
RBFOX3	ENST00000583458.5	TSL:5	c.1020C>T	p.Ala340Ala	synonymous	Exon 13 of 14	ENSP00000464186.1	J3QRF4

Frequencies

GnomAD3 genomes

AF:

0.0000397

AC:

AN:

151298

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000499

AC:

AN:

80240

AF XY:

0.0000680

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000621

AC:

AN:

1305204

Hom.:

Cov.:

AF XY:

0.0000626

AC XY:

AN XY:

639198

show subpopulations

African (AFR)

AF:

0.0000387

AC:

AN:

25818

American (AMR)

AF:

0.00

AC:

AN:

20200

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22428

East Asian (EAS)

AF:

0.00

AC:

AN:

28288

South Asian (SAS)

AF:

0.00

AC:

AN:

68362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5064

European-Non Finnish (NFE)

AF:

0.0000772

AC:

AN:

1036886

Other (OTH)

AF:

0.00

AC:

AN:

53878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000396

AC:

AN:

151414

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

73994

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41262

American (AMR)

AF:

0.00

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000197

AC:

AN:

5084

South Asian (SAS)

AF:

0.00

AC:

AN:

4770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000590

AC:

AN:

67782

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000843

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Idiopathic generalized epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

9.7

(source)

DANN

Benign

0.77

PhyloP100

0.12

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over