chr10-129962088-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 Gene-Disease associations (from GenCC):

• hypotonia, ataxia, and delayed development syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

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.411+83T>C		intron	N/A	NP_001362309.1
	EBF3	NM_001375379.1		c.411+83T>C		intron	N/A	NP_001362308.1
	EBF3	NM_001375389.1		c.411+83T>C		intron	N/A	NP_001362318.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF3	ENST00000440978.2	TSL:3 MANE Select	c.411+83T>C		intron	N/A	ENSP00000387543.2
	EBF3	ENST00000368648.8	TSL:1	c.411+83T>C		intron	N/A	ENSP00000357637.3
	EBF3	ENST00000355311.10	TSL:5	c.411+83T>C		intron	N/A	ENSP00000347463.4

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

African (AFR) AF: 0.338 AC: 9191 AN: 27180

American (AMR) AF: 0.575 AC: 23280 AN: 40498

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 14813 AN: 23406

East Asian (EAS) AF: 0.408 AC: 15539 AN: 38066

South Asian (SAS) AF: 0.600 AC: 46228 AN: 77104

European-Finnish (FIN) AF: 0.699 AC: 36994 AN: 52902

Middle Eastern (MID) AF: 0.545 AC: 2773 AN: 5088

European-Non Finnish (NFE) AF: 0.612 AC: 522322 AN: 853496

Other (OTH) AF: 0.590 AC: 29834 AN: 50526

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

African (AFR) AF: 0.339 AC: 14054 AN: 41450

American (AMR) AF: 0.557 AC: 8508 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2175 AN: 3470

East Asian (EAS) AF: 0.424 AC: 2188 AN: 5156

South Asian (SAS) AF: 0.602 AC: 2898 AN: 4816

European-Finnish (FIN) AF: 0.710 AC: 7510 AN: 10572

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.608 AC: 41331 AN: 67964

Other (OTH) AF: 0.559 AC: 1181 AN: 2114

Alfa AF: 0.576 Hom.: 67739

Bravo AF: 0.514

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.69
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs573370; hg19: chr10-131760352;