chr10-129852137-T-C

Variant names:

• chr10-129852137-T-C
• rs11016976
• NM_001375380.1:c.1040-3657A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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=-0.48).
• 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 rank	MANE	Protein	UniProt
EBF3	NM_001375380.1	c.1040-3657A>G		intron_variant	Intron 10 of 16	ENST00000440978.2	NP_001362309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBF3	ENST00000440978.2	c.1040-3657A>G		intron_variant	Intron 10 of 16	3	NM_001375380.1	ENSP00000387543.2

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

African (AFR) AF: 0.136 AC: 5630 AN: 41510

American (AMR) AF: 0.182 AC: 2786 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3466

East Asian (EAS) AF: 0.120 AC: 619 AN: 5176

South Asian (SAS) AF: 0.192 AC: 924 AN: 4818

European-Finnish (FIN) AF: 0.0940 AC: 998 AN: 10612

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9044 AN: 67986

Other (OTH) AF: 0.161 AC: 339 AN: 2112

Alfa AF: 0.140 Hom.: 4389

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
PhyloP100		1.3
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: rs11016976; hg19: chr10-131650401;