10-129903661-A-G

Variant names:

• chr10-129903661-A-G
• rs4751143
• NM_001375380.1:c.555-25812T>C

Variant summary

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

The NM_001375380.1(EBF3):​c.555-25812T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,044 control chromosomes in the GnomAD database, including 14,247 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 0.42 (14247 hom., cov: 32)
• Consequence: EBF3 NM_001375380.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBF3	NM_001375380.1	c.555-25812T>C		intron_variant	Intron 6 of 16	ENST00000440978.2	NP_001362309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBF3	ENST00000440978.2	c.555-25812T>C		intron_variant	Intron 6 of 16	3	NM_001375380.1	ENSP00000387543.2

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64269 AN: 151926 Hom.: 14242 Cov.: 32

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.423 AC: 64306 AN: 152044 Hom.: 14247 Cov.: 32 AF XY: 0.425 AC XY: 31616 AN XY: 74324

African (AFR) AF: 0.283 AC: 11737 AN: 41488

American (AMR) AF: 0.494 AC: 7554 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1804 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2159 AN: 5144

South Asian (SAS) AF: 0.427 AC: 2054 AN: 4814

European-Finnish (FIN) AF: 0.512 AC: 5415 AN: 10566

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32079 AN: 67956

Other (OTH) AF: 0.430 AC: 908 AN: 2114

Alfa AF: 0.458 Hom.: 62072

Bravo AF: 0.416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.97
DANN	Benign	0.46
PhyloP100		-0.10
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: rs4751143; hg19: chr10-131701925;