Variant 10-129840309-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001375380.1(EBF3):c.1695C>T(p.Pro565=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,591,842 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 2 hom. )

Consequence

EBF3
NM_001375380.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.156

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 10-129840309-G-A is Benign according to our data. Variant chr10-129840309-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 789310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.156 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00119 (182/152362) while in subpopulation NFE AF= 0.00218 (148/68034). AF 95% confidence interval is 0.00189. There are 0 homozygotes in gnomad4. There are 70 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 182 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBF3	NM_001375380.1 linkuse as main transcript	c.1695C>T	p.Pro565=	synonymous_variant	15/17	ENST00000440978.2	NP_001362309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBF3	ENST00000440978.2 linkuse as main transcript	c.1695C>T	p.Pro565=	synonymous_variant	15/17	3	NM_001375380.1	ENSP00000387543
EBF3	ENST00000368648.8 linkuse as main transcript	c.1560C>T	p.Pro520=	synonymous_variant	16/17	1		ENSP00000357637	A1	Q9H4W6-2
EBF3	ENST00000355311.10 linkuse as main transcript	c.1695C>T	p.Pro565=	synonymous_variant	15/16	5		ENSP00000347463	P4	Q9H4W6-1
EBF3	ENST00000675373.1 linkuse as main transcript	n.1232C>T		non_coding_transcript_exon_variant	12/14

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

182

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00218

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000898

AC:

190

AN:

211674

Hom.:

AF XY:

0.000888

AC XY:

101

AN XY:

113680

show subpopulations

Gnomad AFR exome

AF:

0.000551

Gnomad AMR exome

AF:

0.000197

Gnomad ASJ exome

AF:

0.000216

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000380

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00184

Gnomad OTH exome

AF:

0.000561

GnomAD4 exome

AF:

0.00180

AC:

2589

AN:

1439480

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

1217

AN XY:

713732

show subpopulations

Gnomad4 AFR exome

AF:

0.000271

Gnomad4 AMR exome

AF:

0.000387

Gnomad4 ASJ exome

AF:

0.000156

Gnomad4 EAS exome

AF:

0.000361

Gnomad4 SAS exome

AF:

0.0000849

Gnomad4 FIN exome

AF:

0.000136

Gnomad4 NFE exome

AF:

0.00223

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00119

AC:

182

AN:

152362

Hom.:

Cov.:

AF XY:

0.000940

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00218

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.00127

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	EBF3: BP4, BP7, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over