10-129962088-A-G

Variant names:

• chr10-129962088-A-G
• rs573370
• NM_001375380.1:c.411+83T>C

Variant summary

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

The NM_001375380.1(EBF3):​c.411+83T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 1,320,292 control chromosomes in the GnomAD database, including 235,520 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 0.53 (22723 hom., cov: 32)
  • Exomes 𝑓: 0.60 (212797 hom.)
• Consequence: EBF3 NM_001375380.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBF3	NM_001375380.1	c.411+83T>C		intron_variant	Intron 4 of 16	ENST00000440978.2	NP_001362309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBF3	ENST00000440978.2	c.411+83T>C		intron_variant	Intron 4 of 16	3	NM_001375380.1	ENSP00000387543.2
EBF3	ENST00000368648.8	c.411+83T>C		intron_variant	Intron 5 of 16	1		ENSP00000357637.3
EBF3	ENST00000355311.10	c.411+83T>C		intron_variant	Intron 4 of 15	5		ENSP00000347463.4
EBF3	ENST00000682649.1	n.361+83T>C		intron_variant	Intron 4 of 11

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80628 AN: 151908 Hom.: 22708 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.600 AC: 700974 AN: 1168266 Hom.: 212797 AF XY: 0.601 AC XY: 355913 AN XY: 592170

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.575

Gnomad4 ASJ exome AF: 0.633

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.699

Gnomad4 NFE exome AF: 0.612

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.531 AC: 80666 AN: 152026 Hom.: 22723 Cov.: 32 AF XY: 0.536 AC XY: 39792 AN XY: 74286

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.559

Alfa AF: 0.594 Hom.: 40190

Bravo AF: 0.514

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.69

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: rs573370; hg19: chr10-131760352;