rs1446440015

Variant names:

• chr5-158708078-C-A
• rs1446440015
• NM_024007.5:c.1645G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-158708078-C-A
• chr5-158708078-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_024007.5(EBF1):​c.1645G>T​(p.Val549Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000492 in 1,421,540 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. V549I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: EBF1 NM_024007.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.38367423).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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.1645G>T	p.Val549Phe	missense	Exon 15 of 16	NP_076870.1	Q9UH73-1
	EBF1	NM_001324101.2		c.1648G>T	p.Val550Phe	missense	Exon 15 of 17	NP_001311030.1
	EBF1	NM_001324103.2		c.1645G>T	p.Val549Phe	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.1645G>T	p.Val549Phe	missense	Exon 15 of 16	ENSP00000322898.6	Q9UH73-1
	EBF1	ENST00000380654.8	TSL:1	c.1552G>T	p.Val518Phe	missense	Exon 14 of 15	ENSP00000370029.4	Q9UH73-2
	EBF1	ENST00000964682.1		c.1768G>T	p.Val590Phe	missense	Exon 16 of 17	ENSP00000634741.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 188170 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000492 AC: 7 AN: 1421540 Hom.: 0 Cov.: 31 AF XY: 0.00000569 AC XY: 4 AN XY: 702870

African (AFR) AF: 0.00 AC: 0 AN: 32726

American (AMR) AF: 0.00 AC: 0 AN: 38974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25386

East Asian (EAS) AF: 0.00 AC: 0 AN: 37988

South Asian (SAS) AF: 0.00 AC: 0 AN: 80624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5226

European-Non Finnish (NFE) AF: 0.00000550 AC: 6 AN: 1090716

Other (OTH) AF: 0.0000170 AC: 1 AN: 58920

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.60	N
PhyloP100		5.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.21
Sift	Benign	0.46	T
Sift4G	Benign	0.078	T
Polyphen		0.36	B
Vest4		0.83
MutPred		0.22		Loss of MoRF binding (P = 0.1092)
MVP		0.31
MPC		0.56
ClinPred		0.74	D
GERP RS		5.1
Varity_R		0.25
gMVP		0.89
Mutation Taster		=10/90	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: rs1446440015; hg19: chr5-158135086; COSMIC: COSV58177087; COSMIC: COSV58177087;