NM_024007.5:c.1364A>G

Variant names:

• chr5-158712975-T-C
• rs1010503968
• NM_024007.5:c.1364A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024007.5(EBF1):​c.1364A>G​(p.Asn455Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000134 in 1,487,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: EBF1 NM_024007.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1598897).

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.1364A>G	p.Asn455Ser	missense	Exon 13 of 16	NP_076870.1	Q9UH73-1
	EBF1	NM_001324101.2		c.1367A>G	p.Asn456Ser	missense	Exon 13 of 17	NP_001311030.1
	EBF1	NM_001324103.2		c.1364A>G	p.Asn455Ser	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.1364A>G	p.Asn455Ser	missense	Exon 13 of 16	ENSP00000322898.6	Q9UH73-1
	EBF1	ENST00000380654.8	TSL:1	c.1271A>G	p.Asn424Ser	missense	Exon 12 of 15	ENSP00000370029.4	Q9UH73-2
	EBF1	ENST00000964682.1		c.1487A>G	p.Asn496Ser	missense	Exon 14 of 17	ENSP00000634741.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1335724 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 652946

African (AFR) AF: 0.00 AC: 0 AN: 29672

American (AMR) AF: 0.00 AC: 0 AN: 32532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21156

East Asian (EAS) AF: 0.00 AC: 0 AN: 35676

South Asian (SAS) AF: 0.00 AC: 0 AN: 65380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5228

European-Non Finnish (NFE) AF: 9.60e-7 AC: 1 AN: 1041276

Other (OTH) AF: 0.00 AC: 0 AN: 54720

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.060
Sift	Benign	0.35	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.27
MutPred		0.19		Gain of sheet (P = 0.0344)
MVP		0.63
MPC		0.33
ClinPred		0.62	D
GERP RS		2.2
Varity_R		0.044
gMVP		0.41
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs1010503968; hg19: chr5-158139983;