chr5-158712988-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024007.5(EBF1):ā€‹c.1351T>Cā€‹(p.Ser451Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000335 in 1,494,390 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000030 ( 0 hom. )

Consequence

EBF1
NM_024007.5 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86
Variant links:
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17662433).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EBF1NM_024007.5 linkuse as main transcriptc.1351T>C p.Ser451Pro missense_variant 13/16 ENST00000313708.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EBF1ENST00000313708.11 linkuse as main transcriptc.1351T>C p.Ser451Pro missense_variant 13/161 NM_024007.5 P1Q9UH73-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152132
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000536
AC:
1
AN:
186718
Hom.:
0
AF XY:
0.00000997
AC XY:
1
AN XY:
100322
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000112
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000298
AC:
4
AN:
1342258
Hom.:
0
Cov.:
31
AF XY:
0.00000304
AC XY:
2
AN XY:
657378
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000287
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152132
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

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 submitterclinical testingAmbry GeneticsNov 13, 2023The c.1351T>C (p.S451P) alteration is located in exon 13 (coding exon 13) of the EBF1 gene. This alteration results from a T to C substitution at nucleotide position 1351, causing the serine (S) at amino acid position 451 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
.;T;.;.
Eigen
Benign
-0.069
Eigen_PC
Benign
0.054
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.89
D;T;D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.18
T;T;T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Uncertain
2.4
.;M;.;.
MutationTaster
Benign
0.55
D;N;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-2.7
.;D;D;N
REVEL
Benign
0.10
Sift
Uncertain
0.010
.;D;D;T
Sift4G
Uncertain
0.052
T;D;T;D
Polyphen
0.0
.;B;B;.
Vest4
0.47, 0.51, 0.45
MutPred
0.24
.;Loss of sheet (P = 0.0181);.;.;
MVP
0.34
MPC
0.54
ClinPred
0.56
D
GERP RS
4.8
Varity_R
0.48
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1170847073; hg19: chr5-158139996; API