chr10-129841042-T-C
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_001375380.1(EBF3):c.1373-10A>G 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 0.000691 in 1,509,798 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.0017 ( 2 hom., cov: 22)
Exomes 𝑓: 0.00059 ( 0 hom. )
Consequence
EBF3
NM_001375380.1 splice_polypyrimidine_tract, intron
NM_001375380.1 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0009954
2
Clinical Significance
Conservation
PhyloP100: -0.329
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
Variant 10-129841042-T-C is Benign according to our data. Variant chr10-129841042-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3033969.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00173 (236/136128) while in subpopulation AFR AF= 0.00227 (87/38248). AF 95% confidence interval is 0.00189. There are 2 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
High AC in GnomAd at 234 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EBF3 | NM_001375380.1 | c.1373-10A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000440978.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EBF3 | ENST00000440978.2 | c.1373-10A>G | splice_polypyrimidine_tract_variant, intron_variant | 3 | NM_001375380.1 | ||||
EBF3 | ENST00000368648.8 | c.1346-10A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | A1 | ||||
EBF3 | ENST00000355311.10 | c.1373-10A>G | splice_polypyrimidine_tract_variant, intron_variant | 5 | P4 | ||||
EBF3 | ENST00000675373.1 | n.1018-10A>G | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00172 AC: 234AN: 136046Hom.: 2 Cov.: 22
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GnomAD3 exomes AF: 0.00269 AC: 365AN: 135842Hom.: 0 AF XY: 0.00288 AC XY: 207AN XY: 71918
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GnomAD4 exome AF: 0.000587 AC: 807AN: 1373670Hom.: 0 Cov.: 38 AF XY: 0.000663 AC XY: 448AN XY: 675854
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GnomAD4 genome ? AF: 0.00173 AC: 236AN: 136128Hom.: 2 Cov.: 22 AF XY: 0.00157 AC XY: 102AN XY: 64790
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
EBF3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 17, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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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