8-25861178-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_022659.4(EBF2):​c.1213G>A​(p.Val405Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00007 in 1,613,790 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: 0.000070 ( 0 hom. )

Consequence

EBF2
NM_022659.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15
Variant links:
Genes affected
EBF2 (HGNC:19090): (EBF transcription factor 2) The protein encoded by this gene belongs to the COE (Collier/Olf/EBF) family of non-basic, helix-loop-helix transcription factors that have a well conserved DNA binding domain. The COE family proteins play an important role in variety of developmental processes. Studies in mouse suggest that this gene may be involved in the differentiation of osteoblasts. [provided by RefSeq, Oct 2011]

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=0.313448).
BS2
High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EBF2NM_022659.4 linkc.1213G>A p.Val405Ile missense_variant Exon 13 of 16 ENST00000520164.6 NP_073150.2 Q9HAK2-1B7Z934B2RNT0
LOC102723395XR_001745848.2 linkn.214-8801C>T intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EBF2ENST00000520164.6 linkc.1213G>A p.Val405Ile missense_variant Exon 13 of 16 2 NM_022659.4 ENSP00000430241.1 Q9HAK2-1
EBF2ENST00000408929.7 linkc.769G>A p.Val257Ile missense_variant Exon 12 of 15 2 ENSP00000386178.3 B7Z934
EBF2ENST00000535548.1 linkc.406G>A p.Val136Ile missense_variant Exon 5 of 9 2 ENSP00000437909.1 Q9HAK2-2

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152136
Hom.:
0
Cov.:
32
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000562
AC:
14
AN:
248994
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135078
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000974
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000698
AC:
102
AN:
1461654
Hom.:
0
Cov.:
31
AF XY:
0.0000743
AC XY:
54
AN XY:
727124
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000854
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152136
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74314
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:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.0000567
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000120
AC:
1
ExAC
AF:
0.0000496
AC:
6
EpiCase
AF:
0.000164
EpiControl
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
Jan 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1213G>A (p.V405I) alteration is located in exon 13 (coding exon 13) of the EBF2 gene. This alteration results from a G to A substitution at nucleotide position 1213, causing the valine (V) at amino acid position 405 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
0.089
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;T;.
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.31
T;T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
1.9
L;.;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.51
N;N;N
REVEL
Benign
0.13
Sift
Benign
0.037
D;D;T
Sift4G
Benign
0.19
T;T;T
Polyphen
0.97
D;.;.
Vest4
0.42
MVP
0.26
MPC
1.2
ClinPred
0.22
T
GERP RS
5.3
Varity_R
0.15
gMVP
0.57

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: rs369134736; hg19: chr8-25718694; COSMIC: COSV68775879; API