chr5-158712292-C-G

Position:

• chr5-158712292-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024007.5(EBF1):​c.1411G>C​(p.Val471Leu) 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: 5.02

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22770032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBF1	NM_024007.5	c.1411G>C	p.Val471Leu	missense_variant	14/16	ENST00000313708.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBF1	ENST00000313708.11	c.1411G>C	p.Val471Leu	missense_variant	14/16	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

May 26, 2024

The c.1411G>C (p.V471L) alteration is located in exon 14 (coding exon 14) of the EBF1 gene. This alteration results from a G to C substitution at nucleotide position 1411, causing the valine (V) at amino acid position 471 to be replaced by a leucine (L). 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	0.17
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.39	.;T;.
Eigen	Benign	-0.00037
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	.;M;.
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.79	.;N;N
REVEL	Benign	0.17
Sift	Benign	0.49	.;T;T
Sift4G	Benign	0.69	T;T;T
Polyphen		0.012	.;B;B
Vest4		0.63, 0.64
MutPred		0.11		.;Gain of sheet (P = 0.0827);.;
MVP		0.44
MPC		0.41
ClinPred		0.49	T
GERP RS		4.8
Varity_R		0.13
gMVP		0.70

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: chr5-158139300;