NM_001375380.1:c.555-9559A>G

Variant names:

• chr10-129887408-T-C
• rs1334011
• NM_001375380.1:c.555-9559A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001375380.1(EBF3):​c.555-9559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,048 control chromosomes in the GnomAD database, including 17,786 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (17786 hom., cov: 33)
• Consequence: EBF3 NM_001375380.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483
• Publications: 2 publications found

Genes affected

EBF3 (HGNC:19087): (EBF transcription factor 3) This gene encodes a member of the early B-cell factor (EBF) family of DNA binding transcription factors. EBF proteins are involved in B-cell differentiation, bone development and neurogenesis, and may also function as tumor suppressors. The encoded protein inhibits cell survival through the regulation of genes involved in cell cycle arrest and apoptosis, and aberrant methylation or deletion of this gene may play a role in multiple malignancies including glioblastoma multiforme and gastric carcinoma. [provided by RefSeq, Sep 2011]

EBF3 Gene-Disease associations (from GenCC):

• hypotonia, ataxia, and delayed development syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375380.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF3	NM_001375380.1	MANE Select	c.555-9559A>G		intron	N/A	NP_001362309.1
	EBF3	NM_001375379.1		c.555-9559A>G		intron	N/A	NP_001362308.1
	EBF3	NM_001375389.1		c.555-9559A>G		intron	N/A	NP_001362318.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF3	ENST00000440978.2	TSL:3 MANE Select	c.555-9559A>G		intron	N/A	ENSP00000387543.2
	EBF3	ENST00000368648.8	TSL:1	c.555-9559A>G		intron	N/A	ENSP00000357637.3
	EBF3	ENST00000355311.10	TSL:5	c.555-9559A>G		intron	N/A	ENSP00000347463.4

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71572 AN: 151930 Hom.: 17782 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.442

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.471 AC: 71612 AN: 152048 Hom.: 17786 Cov.: 33 AF XY: 0.470 AC XY: 34929 AN XY: 74306

African (AFR) AF: 0.639 AC: 26496 AN: 41490

American (AMR) AF: 0.437 AC: 6677 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1298 AN: 3468

East Asian (EAS) AF: 0.506 AC: 2607 AN: 5156

South Asian (SAS) AF: 0.391 AC: 1884 AN: 4818

European-Finnish (FIN) AF: 0.394 AC: 4157 AN: 10546

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27083 AN: 67978

Other (OTH) AF: 0.441 AC: 931 AN: 2110

Alfa AF: 0.436 Hom.: 10744

Bravo AF: 0.482

Asia WGS AF: 0.460 AC: 1600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	14
DANN	Benign	0.76
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs1334011; hg19: chr10-131685672;