10-129852137-T-C

Position:

• chr10-129852137-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375380.1(EBF3):​c.1040-3657A>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 152,178 control chromosomes in the GnomAD database, including 1,563 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 (1563 hom., cov: 33)
• Consequence: EBF3 NM_001375380.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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=-0.48).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBF3	NM_001375380.1	c.1040-3657A>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.1040-3657A>G		intron_variant		3	NM_001375380.1	ENSP00000387543

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21111 AN: 152060 Hom.: 1564 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0940

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.139 AC: 21126 AN: 152178 Hom.: 1563 Cov.: 33 AF XY: 0.139 AC XY: 10342 AN XY: 74410

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.0940

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.161

Alfa AF: 0.144 Hom.: 1781

Bravo AF: 0.148

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.8
DANN	Benign	0.70

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: rs11016976; hg19: chr10-131650401;