chr5-158708039-C-T

Variant summary

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

The NM_024007.5(EBF1):​c.1684G>A​(p.Val562Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,553,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

EBF1
NM_024007.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
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=0.17166075).
BS2
High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EBF1NM_024007.5 linkuse as main transcriptc.1684G>A p.Val562Ile missense_variant 15/16 ENST00000313708.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EBF1ENST00000313708.11 linkuse as main transcriptc.1684G>A p.Val562Ile missense_variant 15/161 NM_024007.5 P1Q9UH73-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152142
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000187
AC:
3
AN:
160422
Hom.:
0
AF XY:
0.0000118
AC XY:
1
AN XY:
84460
show subpopulations
Gnomad AFR exome
AF:
0.000108
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000435
Gnomad FIN exome
AF:
0.0000644
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
22
AN:
1401334
Hom.:
0
Cov.:
31
AF XY:
0.0000174
AC XY:
12
AN XY:
691454
show subpopulations
Gnomad4 AFR exome
AF:
0.0000628
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000276
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.0000201
Gnomad4 NFE exome
AF:
0.00000648
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152260
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.00000875
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 GeneticsOct 13, 2023The c.1684G>A (p.V562I) alteration is located in exon 15 (coding exon 15) of the EBF1 gene. This alteration results from a G to A substitution at nucleotide position 1684, causing the valine (V) at amino acid position 562 to be replaced by an isoleucine (I). 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
0.11
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.38
CADD
Pathogenic
27
DANN
Benign
0.96
DEOGEN2
Benign
0.16
.;T;.;.
Eigen
Benign
-0.026
Eigen_PC
Benign
0.17
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
D;D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.17
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
.;L;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-0.20
.;N;N;N
REVEL
Benign
0.13
Sift
Benign
0.47
.;T;T;T
Sift4G
Benign
0.27
T;T;T;T
Polyphen
0.0030, 0.0020
.;B;B;.
Vest4
0.52, 0.52, 0.50
MutPred
0.18
.;Gain of catalytic residue at P564 (P = 0.0339);.;.;
MVP
0.45
MPC
0.35
ClinPred
0.15
T
GERP RS
5.1
Varity_R
0.063
gMVP
0.47

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: rs764892787; hg19: chr5-158135047; COSMIC: COSV104625248; COSMIC: COSV104625248; API