chr22-35761304-T-G
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001349999.2(RBFOX2):c.872-10A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000274 in 1,614,032 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 Benign (★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 2 hom. )
Consequence
RBFOX2
NM_001349999.2 splice_polypyrimidine_tract, intron
NM_001349999.2 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00001642
2
Clinical Significance
Conservation
PhyloP100: 1.98
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 22-35761304-T-G is Benign according to our data. Variant chr22-35761304-T-G is described in ClinVar as [Benign]. Clinvar id is 740212.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 31 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBFOX2 | NM_001349999.2 | c.872-10A>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000695854.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBFOX2 | ENST00000695854.1 | c.872-10A>C | splice_polypyrimidine_tract_variant, intron_variant | NM_001349999.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152116Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000438 AC: 110AN: 250992Hom.: 0 AF XY: 0.000523 AC XY: 71AN XY: 135660
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GnomAD4 exome AF: 0.000282 AC: 412AN: 1461798Hom.: 2 Cov.: 33 AF XY: 0.000329 AC XY: 239AN XY: 727196
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at