10-129932050-G-C

Variant names:

• chr10-129932050-G-C
• rs10764921
• NM_001375380.1:c.554+25208C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375380.1(EBF3):​c.554+25208C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,076 control chromosomes in the GnomAD database, including 50,186 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 0.81 (50186 hom., cov: 31)
• Consequence: EBF3 NM_001375380.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.219
• Publications: 1 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, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF3	NM_001375380.1	MANE Select	c.554+25208C>G		intron	N/A	NP_001362309.1	H0Y3W9
	EBF3	NM_001375379.1		c.554+25208C>G		intron	N/A	NP_001362308.1	Q9H4W6-1
	EBF3	NM_001375389.1		c.554+25208C>G		intron	N/A	NP_001362318.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF3	ENST00000440978.2	TSL:3 MANE Select	c.554+25208C>G		intron	N/A	ENSP00000387543.2	H0Y3W9
	EBF3	ENST00000368648.8	TSL:1	c.554+25208C>G		intron	N/A	ENSP00000357637.3	Q9H4W6-2
	EBF3	ENST00000904893.1		c.554+25208C>G		intron	N/A	ENSP00000574952.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122870 AN: 151958 Hom.: 50128 Cov.: 31

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.786

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

GnomAD4 genome AF: 0.809 AC: 122990 AN: 152076 Hom.: 50186 Cov.: 31 AF XY: 0.809 AC XY: 60153 AN XY: 74316

African (AFR) AF: 0.903 AC: 37473 AN: 41496

American (AMR) AF: 0.844 AC: 12903 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2655 AN: 3472

East Asian (EAS) AF: 0.956 AC: 4922 AN: 5146

South Asian (SAS) AF: 0.781 AC: 3758 AN: 4814

European-Finnish (FIN) AF: 0.735 AC: 7774 AN: 10584

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50857 AN: 67954

Other (OTH) AF: 0.787 AC: 1660 AN: 2110

Alfa AF: 0.776 Hom.: 5702

Bravo AF: 0.825

Asia WGS AF: 0.874 AC: 3036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.41
PhyloP100		-0.22
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: rs10764921; hg19: chr10-131730314;