dbSNP rs537082559: RBFOX2:c.1138-16C>T (chr22-35746577-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_001349999.2(RBFOX2):c.1138-16C>T variant causes a intron change. The variant allele was found at a frequency of 0.000051 in 1,509,918 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 1 hom. )

Consequence

RBFOX2
NM_001349999.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.76

Publications

0 publications found

Variant links:

Genes affected

RBFOX2 (HGNC:9906): (RNA binding fox-1 homolog 2) This gene is one of several human genes similar to the C. elegans gene Fox-1. This gene encodes an RNA binding protein that is thought to be a key regulator of alternative exon splicing in the nervous system and other cell types. The protein binds to a conserved UGCAUG element found downstream of many alternatively spliced exons and promotes inclusion of the alternative exon in mature transcripts. The protein also interacts with the estrogen receptor 1 transcription factor and regulates estrogen receptor 1 transcriptional activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RBFOX2 Gene-Disease associations (from GenCC):

congenital heart defects, multiple types
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
congenital heart disease
Inheritance: AD Classification: STRONG Submitted by: ClinGen

RBFOX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.16).

BP6

Variant 22-35746577-G-A is Benign according to our data. Variant chr22-35746577-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3603974.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 19 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349999.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBFOX2	NM_001349999.2	MANE Select	c.1138-16C>T	intron	N/A	NP_001336928.2	A0A8Q3WKT3
RBFOX2	NM_001082578.4		c.1150-16C>T	intron	N/A	NP_001076047.2	O43251-8
RBFOX2	NM_001082579.3		c.1147-16C>T	intron	N/A	NP_001076048.2	O43251-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RBFOX2	ENST00000695854.1	MANE Select	c.1138-16C>T	intron	N/A	ENSP00000512219.1	A0A8Q3WKT3
RBFOX2	ENST00000438146.7	TSL:1	c.1150-16C>T	intron	N/A	ENSP00000413035.2	O43251-8
RBFOX2	ENST00000449924.6	TSL:1	c.937-16C>T	intron	N/A	ENSP00000391670.2	O43251-10

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000489

AC:

AN:

183960

AF XY:

0.0000200

show subpopulations

Gnomad AFR exome

AF:

0.000463

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000142

Gnomad EAS exome

AF:

0.0000746

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000427

AC:

AN:

1357704

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

671684

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

30068

American (AMR)

AF:

0.00

AC:

AN:

33586

Ashkenazi Jewish (ASJ)

AF:

0.0000432

AC:

AN:

23142

East Asian (EAS)

AF:

0.0000272

AC:

AN:

36718

South Asian (SAS)

AF:

0.00

AC:

AN:

76652

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51862

Middle Eastern (MID)

AF:

0.000735

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.0000115

AC:

AN:

1044162

Other (OTH)

AF:

0.000107

AC:

AN:

56074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000125

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41530

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000260

Hom.:

Bravo

AF:

0.000117

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

6.8

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

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