5-158713092-C-G

Variant names:

• chr5-158713092-C-G
• rs755850355
• NM_024007.5:c.1247G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024007.5(EBF1):​c.1247G>C​(p.Arg416Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,898 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R416L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EBF1 NM_024007.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1247G>C	p.Arg416Pro	missense	Exon 13 of 16	NP_076870.1	Q9UH73-1
	EBF1	NM_001324101.2		c.1250G>C	p.Arg417Pro	missense	Exon 13 of 17	NP_001311030.1
	EBF1	NM_001324103.2		c.1247G>C	p.Arg416Pro	missense	Exon 13 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.1247G>C	p.Arg416Pro	missense	Exon 13 of 16	ENSP00000322898.6	Q9UH73-1
	EBF1	ENST00000380654.8	TSL:1	c.1154G>C	p.Arg385Pro	missense	Exon 12 of 15	ENSP00000370029.4	Q9UH73-2
	EBF1	ENST00000964682.1		c.1370G>C	p.Arg457Pro	missense	Exon 14 of 17	ENSP00000634741.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444898 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 718156

African (AFR) AF: 0.00 AC: 0 AN: 32786

American (AMR) AF: 0.00 AC: 0 AN: 43210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25740

East Asian (EAS) AF: 0.00 AC: 0 AN: 38800

South Asian (SAS) AF: 0.00 AC: 0 AN: 83592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102416

Other (OTH) AF: 0.00 AC: 0 AN: 59538

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.36
Sift	Benign	0.040	D
Sift4G	Uncertain	0.020	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.47		Gain of catalytic residue at P415 (P = 0.0126)
MVP		0.54
MPC		1.2
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.77
gMVP		0.94
Mutation Taster		=38/62	disease causing

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

Other links and lift over

dbSNP: rs755850355; hg19: chr5-158140100;