chr22-35943494-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001349999.2(RBFOX2):​c.187-4597G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

RBFOX2
NM_001349999.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

2 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBFOX2NM_001349999.2 linkc.187-4597G>T intron_variant Intron 1 of 13 ENST00000695854.1 NP_001336928.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBFOX2ENST00000695854.1 linkc.187-4597G>T intron_variant Intron 1 of 13 NM_001349999.2 ENSP00000512219.1 A0A8Q3WKT3
RBFOX2ENST00000438146.7 linkc.187-4597G>T intron_variant Intron 1 of 13 1 ENSP00000413035.2 O43251-8
RBFOX2ENST00000695807.1 linkn.-84-4597G>T intron_variant Intron 1 of 14 ENSP00000512187.1 A0A8Q3SI31
RBFOX2ENST00000408983.2 linkc.43-4597G>T intron_variant Intron 1 of 5 3 ENSP00000386177.2 B0QYY7

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151990
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151990
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74252
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41316
American (AMR)
AF:
0.00
AC:
0
AN:
15266
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5194
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10596
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68008
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
663

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.29
DANN
Benign
0.38
PhyloP100
-1.3

Splicing

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

Publications

Other links and lift over

dbSNP: rs5750202; hg19: chr22-36339542; API