chr5-158840040-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024007.5(EBF1):​c.625C>T​(p.Arg209Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R209Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

EBF1
NM_024007.5 missense

Scores

11
7
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.844

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EBF1NM_024007.5 linkuse as main transcriptc.625C>T p.Arg209Trp missense_variant 7/16 ENST00000313708.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EBF1ENST00000313708.11 linkuse as main transcriptc.625C>T p.Arg209Trp missense_variant 7/161 NM_024007.5 P1Q9UH73-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGreenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic CenterJun 30, 2023Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
34
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.89
.;D;.;.
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.84
D;D;D;D
MetaSVM
Uncertain
-0.018
T
MutationAssessor
Pathogenic
3.0
.;M;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.92
D
PROVEAN
Pathogenic
-6.9
.;D;D;D
REVEL
Uncertain
0.59
Sift
Pathogenic
0.0
.;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
.;D;D;.
Vest4
0.94, 0.91, 0.90
MutPred
0.54
.;Loss of disorder (P = 0.0334);.;Loss of disorder (P = 0.0334);
MVP
0.93
MPC
2.3
ClinPred
1.0
D
GERP RS
3.5
Varity_R
0.87
gMVP
0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-158267048; COSMIC: COSV58166655; API