chr5-158713033-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_024007.5(EBF1):c.1306G>A(p.Val436Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000367 in 1,578,422 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 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
EBF1
NM_024007.5 missense
NM_024007.5 missense
Scores
3
5
11
Clinical Significance
Conservation
PhyloP100: 6.17
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.27030575).
BS2
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EBF1 | NM_024007.5 | c.1306G>A | p.Val436Met | missense_variant | 13/16 | ENST00000313708.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EBF1 | ENST00000313708.11 | c.1306G>A | p.Val436Met | missense_variant | 13/16 | 1 | NM_024007.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152152Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
11
AN:
152152
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000214 AC: 5AN: 233894Hom.: 0 AF XY: 0.0000237 AC XY: 3AN XY: 126706
GnomAD3 exomes
AF:
AC:
5
AN:
233894
Hom.:
AF XY:
AC XY:
3
AN XY:
126706
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000330 AC: 47AN: 1426270Hom.: 0 Cov.: 30 AF XY: 0.0000254 AC XY: 18AN XY: 707650
GnomAD4 exome
AF:
AC:
47
AN:
1426270
Hom.:
Cov.:
30
AF XY:
AC XY:
18
AN XY:
707650
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74316
GnomAD4 genome
AF:
AC:
11
AN:
152152
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74316
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
2
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 | Aug 08, 2022 | The c.1306G>A (p.V436M) alteration is located in exon 13 (coding exon 13) of the EBF1 gene. This alteration results from a G to A substitution at nucleotide position 1306, causing the valine (V) at amino acid position 436 to be replaced by a methionine (M). 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
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
.;N;N;N
REVEL
Benign
Sift
Benign
.;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.016, 0.12
.;B;B;.
Vest4
0.62, 0.58, 0.60
MVP
MPC
0.45
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at