Variant 5-158713048-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024007.5(EBF1):c.1291G>A(p.Ala431Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,597,976 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

EBF1
NM_024007.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.820

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]

EBF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03487751).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBF1	NM_024007.5 link	c.1291G>A	p.Ala431Thr	missense_variant	13/16	ENST00000313708.11	NP_076870.1	Q9UH73-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBF1	ENST00000313708.11 link	c.1291G>A	p.Ala431Thr	missense_variant	13/16	1	NM_024007.5	ENSP00000322898.6		Q9UH73-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000289

AC:

AN:

242140

Hom.:

AF XY:

0.0000535

AC XY:

AN XY:

130962

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:

0.000173

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00000905

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000249

AC:

AN:

1445854

Hom.:

Cov.:

AF XY:

0.0000334

AC XY:

AN XY:

718750

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000287

Gnomad4 FIN exome

AF:

0.0000941

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.0000671

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000416

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.1291G>A (p.A431T) alteration is located in exon 13 (coding exon 13) of the EBF1 gene. This alteration results from a G to A substitution at nucleotide position 1291, causing the alanine (A) at amino acid position 431 to be replaced by a threonine (T). 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

0.063

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

.;T;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.85

D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.035

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

.;N;.;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

0.87

.;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.53

.;T;T;T

Sift4G

Benign

0.62

T;T;T;T

Polyphen

0.0, 0.0010

.;B;B;.

Vest4

0.47, 0.45, 0.47

MutPred

0.36

.;Loss of sheet (P = 0.0084);.;.;

MVP

0.29

MPC

0.40

ClinPred

0.073

GERP RS

5.0

Varity_R

0.039

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over