Genetic Variant NM_024007.5:c.1306G>T (chr5-158713033-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024007.5(EBF1):c.1306G>T(p.Val436Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,426,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V436M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

EBF1
NM_024007.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.17

Publications

3 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37878582).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024007.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EBF1	NM_024007.5	MANE Select	c.1306G>T	p.Val436Leu	missense	Exon 13 of 16	NP_076870.1	Q9UH73-1
EBF1	NM_001324101.2		c.1309G>T	p.Val437Leu	missense	Exon 13 of 17	NP_001311030.1
EBF1	NM_001324103.2		c.1306G>T	p.Val436Leu	missense	Exon 13 of 17	NP_001311032.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EBF1	ENST00000313708.11	TSL:1 MANE Select	c.1306G>T	p.Val436Leu	missense	Exon 13 of 16	ENSP00000322898.6	Q9UH73-1
EBF1	ENST00000380654.8	TSL:1	c.1213G>T	p.Val405Leu	missense	Exon 12 of 15	ENSP00000370029.4	Q9UH73-2
EBF1	ENST00000964682.1		c.1429G>T	p.Val477Leu	missense	Exon 14 of 17	ENSP00000634741.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1426272

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707650

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32050

American (AMR)

AF:

0.00

AC:

AN:

41386

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25268

East Asian (EAS)

AF:

0.00

AC:

AN:

37858

South Asian (SAS)

AF:

0.00

AC:

AN:

81050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

9.16e-7

AC:

AN:

1091568

Other (OTH)

AF:

0.00

AC:

AN:

58690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.017

MetaRNN

Benign

0.38

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

PhyloP100

6.2

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.76

REVEL

Benign

0.13

Sift

Benign

0.16

Sift4G

Benign

0.23

Polyphen

0.0060

Vest4

0.87

MutPred

0.39

Loss of sheet (P = 0.0104)

MVP

0.63

MPC

0.41

ClinPred

0.76

GERP RS

5.9

Varity_R

0.16

gMVP

0.71

Mutation Taster

=54/46

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over