5-158713033-C-A

Variant names:

• chr5-158713033-C-A
• rs149065953
• NM_024007.5:c.1306G>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17
• Publications: 3 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=0.37878582).

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

Sel.	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

Sel.	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.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426272 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 707650

African (AFR) AF: 0.00 AC: 0 AN: 32050

American (AMR) AF: 0.00 AC: 0 AN: 41386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25268

East Asian (EAS) AF: 0.00 AC: 0 AN: 37858

South Asian (SAS) AF: 0.00 AC: 0 AN: 81050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52776

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5626

European-Non Finnish (NFE) AF: 9.16e-7 AC: 1 AN: 1091568

Other (OTH) AF: 0.00 AC: 0 AN: 58690

GnomAD4 genome Cov.: 32

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	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.2
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.13
Sift	Benign	0.16	T
Sift4G	Benign	0.23	T
Polyphen		0.0060	B
Vest4		0.87
MutPred		0.39		Loss of sheet (P = 0.0104)
MVP		0.63
MPC		0.41
ClinPred		0.76	D
GERP RS		5.9
Varity_R		0.16
gMVP		0.71
Mutation Taster		=54/46	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: rs149065953; hg19: chr5-158140041;