10-129837935-T-A

Variant names:

• chr10-129837935-T-A
• rs1590019771
• ENST00000368648.8:c.1650A>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001375379.1(EBF3):​c.1785A>T​(p.Pro595Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EBF3 NM_001375379.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.616
• Publications: 0 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)

ENSG00000300012 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-129837935-T-A is Benign according to our data. Variant chr10-129837935-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 792335.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.616 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375379.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF3	NM_001375380.1	MANE Select	c.*8A>T		3_prime_UTR	Exon 17 of 17	NP_001362309.1
	EBF3	NM_001375379.1		c.1785A>T	p.Pro595Pro	synonymous	Exon 16 of 16	NP_001362308.1
	EBF3	NM_001375391.1		c.1677A>T	p.Pro559Pro	synonymous	Exon 16 of 16	NP_001362320.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF3	ENST00000368648.8	TSL:1	c.1650A>T	p.Pro550Pro	synonymous	Exon 17 of 17	ENSP00000357637.3
	EBF3	ENST00000440978.2	TSL:3 MANE Select	c.*8A>T		3_prime_UTR	Exon 17 of 17	ENSP00000387543.2
	EBF3	ENST00000355311.10	TSL:5	c.1785A>T	p.Pro595Pro	synonymous	Exon 16 of 16	ENSP00000347463.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.56
PhyloP100		-0.62

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: rs1590019771; hg19: chr10-131636199;