rs12771404

Positions:

• chr10-129901347-T-C
• chr10-129901347-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001375380.1(EBF3):​c.555-23498A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,278 control chromosomes in the GnomAD database, including 1,945 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 0.14 (1945 hom., cov: 33)
• Consequence: EBF3 NM_001375380.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBF3	NM_001375380.1	c.555-23498A>G		intron_variant		ENST00000440978.2	NP_001362309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBF3	ENST00000440978.2	c.555-23498A>G		intron_variant		3	NM_001375380.1	ENSP00000387543

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21217 AN: 152160 Hom.: 1941 Cov.: 33

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.0952

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.139 AC: 21241 AN: 152278 Hom.: 1945 Cov.: 33 AF XY: 0.143 AC XY: 10618 AN XY: 74458

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.0952

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.127

Alfa AF: 0.153 Hom.: 486

Bravo AF: 0.135

Asia WGS AF: 0.163 AC: 566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.85

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: rs12771404; hg19: chr10-131699611;