chr5-158713065-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_024007.5(EBF1):​c.1274C>T​(p.Ala425Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,599,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

EBF1
NM_024007.5 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.16395158).
BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EBF1NM_024007.5 linkuse as main transcriptc.1274C>T p.Ala425Val missense_variant 13/16 ENST00000313708.11 NP_076870.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EBF1ENST00000313708.11 linkuse as main transcriptc.1274C>T p.Ala425Val missense_variant 13/161 NM_024007.5 ENSP00000322898 P1Q9UH73-1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000553
AC:
8
AN:
1447248
Hom.:
0
Cov.:
31
AF XY:
0.00000278
AC XY:
2
AN XY:
719456
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000184
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000144
ExAC
AF:
0.00000824
AC:
1

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 15, 2023The c.1274C>T (p.A425V) alteration is located in exon 13 (coding exon 13) of the EBF1 gene. This alteration results from a C to T substitution at nucleotide position 1274, causing the alanine (A) at amino acid position 425 to be replaced by a valine (V). 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
0.17
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.49
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
.;T;.;.
Eigen
Benign
0.086
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Pathogenic
0.98
D;D;D;D
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.16
T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.6
.;L;.;.
MutationTaster
Benign
0.99
N;N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.4
.;N;N;N
REVEL
Benign
0.069
Sift
Uncertain
0.022
.;D;D;D
Sift4G
Benign
0.078
T;T;T;T
Polyphen
0.0090, 0.0020
.;B;B;.
Vest4
0.50, 0.46, 0.43
MutPred
0.41
.;Loss of sheet (P = 0.0817);.;.;
MVP
0.25
MPC
0.42
ClinPred
0.67
D
GERP RS
5.9
Varity_R
0.075
gMVP
0.33

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: rs762145923; hg19: chr5-158140073; API