10-129867142-G-C

Variant names:

• chr10-129867142-G-C
• rs142165671
• NM_001375380.1:c.1038C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001375380.1(EBF3):​c.1038C>G​(p.Thr346Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,613,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T346T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00088 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (0 hom.)
• Consequence: EBF3 NM_001375380.1 splice_region, synonymous
• Scores: Splicing: ADA: 0.0002761
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.885
• 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-AS1 (HGNC:56218): (EBF3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 10-129867142-G-C is Benign according to our data. Variant chr10-129867142-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 445439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.885 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000881 (134/152176) while in subpopulation NFE AF = 0.00147 (100/68038). AF 95% confidence interval is 0.00124. There are 0 homozygotes in GnomAd4. There are 49 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 134 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375380.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF3	NM_001375380.1	MANE Select	c.1038C>G	p.Thr346Thr	splice_region synonymous	Exon 10 of 17	NP_001362309.1
	EBF3	NM_001375379.1		c.1038C>G	p.Thr346Thr	splice_region synonymous	Exon 10 of 16	NP_001362308.1
	EBF3	NM_001375389.1		c.1038C>G	p.Thr346Thr	splice_region synonymous	Exon 10 of 17	NP_001362318.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF3	ENST00000440978.2	TSL:3 MANE Select	c.1038C>G	p.Thr346Thr	splice_region synonymous	Exon 10 of 17	ENSP00000387543.2
	EBF3	ENST00000368648.8	TSL:1	c.1011C>G	p.Thr337Thr	splice_region synonymous	Exon 11 of 17	ENSP00000357637.3
	EBF3	ENST00000355311.10	TSL:5	c.1038C>G	p.Thr346Thr	splice_region synonymous	Exon 10 of 16	ENSP00000347463.4

Frequencies

GnomAD3 genomes AF: 0.000881 AC: 134 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000736 AC: 184 AN: 249858 AF XY: 0.000850

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.00143

Gnomad OTH exome AF: 0.000658

GnomAD4 exome AF: 0.00161 AC: 2357 AN: 1461254 Hom.: 0 Cov.: 31 AF XY: 0.00158 AC XY: 1150 AN XY: 726938

African (AFR) AF: 0.000419 AC: 14 AN: 33428

American (AMR) AF: 0.000471 AC: 21 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.000169 AC: 9 AN: 53374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00198 AC: 2200 AN: 1111782

Other (OTH) AF: 0.00187 AC: 113 AN: 60364

GnomAD4 genome AF: 0.000881 AC: 134 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.000659 AC XY: 49 AN XY: 74328

African (AFR) AF: 0.000531 AC: 22 AN: 41450

American (AMR) AF: 0.000589 AC: 9 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00147 AC: 100 AN: 68038

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.00126 Hom.: 0

Bravo AF: 0.000945

EpiCase AF: 0.00158

EpiControl AF: 0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EBF3: BP4, BP7, BS1

May 22, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.77
DANN	Benign	0.70
PhyloP100		-0.89
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00028
dbscSNV1_RF	Benign	0.026
SpliceAI score (max)		0.12		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: rs142165671; hg19: chr10-131665406;