5-158708039-C-G

Variant names:

• chr5-158708039-C-G
• rs764892787
• NM_024007.5:c.1684G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024007.5(EBF1):​c.1684G>C​(p.Val562Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V562I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EBF1 NM_024007.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 1 publications found

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

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=0.30738264).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF1	NM_024007.5	MANE Select	c.1684G>C	p.Val562Leu	missense	Exon 15 of 16	NP_076870.1	Q9UH73-1
	EBF1	NM_001324101.2		c.1687G>C	p.Val563Leu	missense	Exon 15 of 17	NP_001311030.1
	EBF1	NM_001324103.2		c.1684G>C	p.Val562Leu	missense	Exon 15 of 17	NP_001311032.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF1	ENST00000313708.11	TSL:1 MANE Select	c.1684G>C	p.Val562Leu	missense	Exon 15 of 16	ENSP00000322898.6	Q9UH73-1
	EBF1	ENST00000380654.8	TSL:1	c.1591G>C	p.Val531Leu	missense	Exon 14 of 15	ENSP00000370029.4	Q9UH73-2
	EBF1	ENST00000964682.1		c.1807G>C	p.Val603Leu	missense	Exon 16 of 17	ENSP00000634741.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.027
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.13
Sift	Benign	0.46	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.71
MutPred		0.19		Loss of sheet (P = 0.1158)
MVP		0.71
MPC		0.42
ClinPred		0.88	D
GERP RS		5.1
Varity_R		0.15
gMVP		0.67
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs764892787; hg19: chr5-158135047;