5-158713078-G-A

Position:

• chr5-158713078-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024007.5(EBF1):​c.1261C>T​(p.Leu421Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EBF1 NM_024007.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.63

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32464644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBF1	NM_024007.5	c.1261C>T	p.Leu421Phe	missense_variant	13/16	ENST00000313708.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBF1	ENST00000313708.11	c.1261C>T	p.Leu421Phe	missense_variant	13/16	1	NM_024007.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2024

The c.1261C>T (p.L421F) alteration is located in exon 13 (coding exon 13) of the EBF1 gene. This alteration results from a C to T substitution at nucleotide position 1261, causing the leucine (L) at amino acid position 421 to be replaced by a phenylalanine (F). 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	0.21
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	.;T;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.0	.;M;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	.;N;N;N
REVEL	Benign	0.093
Sift	Uncertain	0.029	.;D;D;D
Sift4G	Benign	0.21	T;T;T;T
Polyphen		0.36, 0.49	.;B;P;.
Vest4		0.69, 0.65, 0.64
MutPred		0.31		.;Gain of catalytic residue at L421 (P = 0.098);.;.;
MVP		0.26
MPC		0.48
ClinPred		0.81	D
GERP RS		5.0
Varity_R		0.16
gMVP		0.61

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: chr5-158140086;