5-158712157-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_024007.5(EBF1):c.1546G>A(p.Ala516Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,530 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: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
EBF1
NM_024007.5 missense
NM_024007.5 missense
Scores
3
3
13
Clinical Significance
Conservation
PhyloP100: 7.90
Genes affected
EBF1 (HGNC:3126): (EBF transcription factor 1) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27520582).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EBF1 | NM_024007.5 | c.1546G>A | p.Ala516Thr | missense_variant | 14/16 | ENST00000313708.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EBF1 | ENST00000313708.11 | c.1546G>A | p.Ala516Thr | missense_variant | 14/16 | 1 | NM_024007.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249474Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134824
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461336Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726882
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74360
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 17, 2023 | The c.1546G>A (p.A516T) alteration is located in exon 14 (coding exon 14) of the EBF1 gene. This alteration results from a G to A substitution at nucleotide position 1546, causing the alanine (A) at amino acid position 516 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N;N
REVEL
Benign
Sift
Benign
.;T;T
Sift4G
Uncertain
D;D;D
Polyphen
0.0020, 0.0040
.;B;B
Vest4
0.73, 0.70
MutPred
0.25
.;Gain of glycosylation at A516 (P = 0.0028);.;
MVP
MPC
0.41
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at