rs4751143

Positions:

• chr10-129903661-A-G
• chr10-129903661-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EBF3	NM_001375380.1	c.555-25812T>C		intron_variant		ENST00000440978.2	NP_001362309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBF3	ENST00000440978.2	c.555-25812T>C		intron_variant		3	NM_001375380.1	ENSP00000387543

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

Gnomad4 AFR AF: 0.283

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.430

Alfa AF: 0.464 Hom.: 26301

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4751143; hg19: chr10-131701925;