chr10-129842113-T-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_001375380.1(EBF3):c.1372+3A>G variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.0000285 in 1,614,076 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
EBF3
NM_001375380.1 splice_donor_region, intron
NM_001375380.1 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.9075
2
Clinical Significance
Conservation
PhyloP100: 3.73
Genes affected
EBF3 (HGNC:19087): (EBF transcription factor 3) This gene encodes a member of the early B-cell factor (EBF) family of DNA binding transcription factors. EBF proteins are involved in B-cell differentiation, bone development and neurogenesis, and may also function as tumor suppressors. The encoded protein inhibits cell survival through the regulation of genes involved in cell cycle arrest and apoptosis, and aberrant methylation or deletion of this gene may play a role in multiple malignancies including glioblastoma multiforme and gastric carcinoma. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BS1
?
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000308 (45/1461870) while in subpopulation MID AF= 0.00104 (6/5768). AF 95% confidence interval is 0.000453. There are 0 homozygotes in gnomad4_exome. There are 24 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAdExome at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EBF3 | NM_001375380.1 | c.1372+3A>G | splice_donor_region_variant, intron_variant | ENST00000440978.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EBF3 | ENST00000440978.2 | c.1372+3A>G | splice_donor_region_variant, intron_variant | 3 | NM_001375380.1 | ||||
EBF3 | ENST00000368648.8 | c.1345+3A>G | splice_donor_region_variant, intron_variant | 1 | A1 | ||||
EBF3 | ENST00000355311.10 | c.1372+3A>G | splice_donor_region_variant, intron_variant | 5 | P4 | ||||
EBF3 | ENST00000675373.1 | n.1017+3A>G | splice_donor_region_variant, intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251376Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135854
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GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461870Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727238
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypotonia, ataxia, and delayed development syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 03, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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