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GeneBe

10-129840261-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001375380.1(EBF3):c.1743C>T(p.Asn581=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,530,460 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000086 ( 1 hom. )

Consequence

EBF3
NM_001375380.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.498
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-129840261-G-A is Benign according to our data. Variant chr10-129840261-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 755545.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.498 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000663 (10/150916) while in subpopulation AMR AF= 0.000132 (2/15178). AF 95% confidence interval is 0.0000476. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EBF3NM_001375380.1 linkuse as main transcriptc.1743C>T p.Asn581= synonymous_variant 15/17 ENST00000440978.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EBF3ENST00000440978.2 linkuse as main transcriptc.1743C>T p.Asn581= synonymous_variant 15/173 NM_001375380.1
EBF3ENST00000368648.8 linkuse as main transcriptc.1608C>T p.Asn536= synonymous_variant 16/171 A1Q9H4W6-2
EBF3ENST00000355311.10 linkuse as main transcriptc.1743C>T p.Asn581= synonymous_variant 15/165 P4Q9H4W6-1
EBF3ENST00000675373.1 linkuse as main transcriptn.1280C>T non_coding_transcript_exon_variant 12/14

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000663
AC:
10
AN:
150916
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000443
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000961
AC:
19
AN:
197612
Hom.:
0
AF XY:
0.000123
AC XY:
13
AN XY:
105426
show subpopulations
Gnomad AFR exome
AF:
0.000166
Gnomad AMR exome
AF:
0.0000344
Gnomad ASJ exome
AF:
0.000111
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000237
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000107
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000863
AC:
119
AN:
1379544
Hom.:
1
Cov.:
37
AF XY:
0.0000996
AC XY:
68
AN XY:
682560
show subpopulations
Gnomad4 AFR exome
AF:
0.0000634
Gnomad4 AMR exome
AF:
0.0000261
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000321
Gnomad4 FIN exome
AF:
0.0000226
Gnomad4 NFE exome
AF:
0.0000770
Gnomad4 OTH exome
AF:
0.000126
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000663
AC:
10
AN:
150916
Hom.:
0
Cov.:
33
AF XY:
0.0000678
AC XY:
5
AN XY:
73734
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000443
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000773
Hom.:
0
Bravo
AF:
0.0000793

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
5.4
Dann
Benign
0.89

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.

Other links and lift over

dbSNP: rs7092828; hg19: chr10-131638525; COSMIC: COSV62475242; COSMIC: COSV62475242; API