NM_001375380.1:c.636+2046G>A

Variant names:

• chr10-129875722-C-T
• rs9804200
• NM_001375380.1:c.636+2046G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375380.1(EBF3):​c.636+2046G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,154 control chromosomes in the GnomAD database, including 31,676 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 0.64 (31676 hom., cov: 33)
• Consequence: EBF3 NM_001375380.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.686 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.636+2046G>A		intron	N/A	NP_001362309.1
	EBF3	NM_001375379.1		c.636+2046G>A		intron	N/A	NP_001362308.1
	EBF3	NM_001375389.1		c.636+2046G>A		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.636+2046G>A		intron	N/A	ENSP00000387543.2
	EBF3	ENST00000368648.8	TSL:1	c.636+2046G>A		intron	N/A	ENSP00000357637.3
	EBF3	ENST00000355311.10	TSL:5	c.636+2046G>A		intron	N/A	ENSP00000347463.4

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97740 AN: 152036 Hom.: 31664 Cov.: 33

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.643 AC: 97785 AN: 152154 Hom.: 31676 Cov.: 33 AF XY: 0.639 AC XY: 47558 AN XY: 74378

African (AFR) AF: 0.585 AC: 24282 AN: 41512

American (AMR) AF: 0.618 AC: 9447 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2604 AN: 3470

East Asian (EAS) AF: 0.479 AC: 2462 AN: 5142

South Asian (SAS) AF: 0.536 AC: 2584 AN: 4824

European-Finnish (FIN) AF: 0.678 AC: 7186 AN: 10592

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 47013 AN: 68004

Other (OTH) AF: 0.651 AC: 1374 AN: 2110

Alfa AF: 0.678 Hom.: 43888

Bravo AF: 0.641

Asia WGS AF: 0.538 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.12
DANN	Benign	0.34
PhyloP100		-1.4
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: rs9804200; hg19: chr10-131673986;