chr5-158713074-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_024007.5(EBF1):​c.1265C>T​(p.Pro422Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000484 in 1,446,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

EBF1
NM_024007.5 missense

Scores

3
12
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.98
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 -4 ACMG points.

BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EBF1NM_024007.5 linkuse as main transcriptc.1265C>T p.Pro422Leu missense_variant 13/16 ENST00000313708.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EBF1ENST00000313708.11 linkuse as main transcriptc.1265C>T p.Pro422Leu missense_variant 13/161 NM_024007.5 P1Q9UH73-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000413
AC:
1
AN:
242124
Hom.:
0
AF XY:
0.00000763
AC XY:
1
AN XY:
130994
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:
0.00000906
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000484
AC:
7
AN:
1446734
Hom.:
0
Cov.:
30
AF XY:
0.00000556
AC XY:
4
AN XY:
719226
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:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000453
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
Cov.:
32

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 GeneticsDec 16, 2023The c.1265C>T (p.P422L) 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 1265, causing the proline (P) at amino acid position 422 to be replaced by a leucine (L). 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
Uncertain
0.37
BayesDel_addAF
Uncertain
0.086
D
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.68
.;D;.;.
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.74
D;D;D;D
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.4
.;M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-6.1
.;D;D;D
REVEL
Uncertain
0.32
Sift
Uncertain
0.0030
.;D;D;D
Sift4G
Uncertain
0.024
D;D;D;D
Polyphen
0.15, 0.16
.;B;B;.
Vest4
0.71, 0.69
MutPred
0.60
.;Loss of disorder (P = 0.0617);.;.;
MVP
0.37
MPC
0.83
ClinPred
0.97
D
GERP RS
5.9
Varity_R
0.35
gMVP
0.55

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: rs774052785; hg19: chr5-158140082; API