rs12771404

Variant names:

• chr10-129901347-T-C
• rs12771404
• NM_001375380.1:c.555-23498A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-129901347-T-C
• chr10-129901347-T-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001375380.1(EBF3):​c.555-23498A>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 152,278 control chromosomes in the GnomAD database, including 1,945 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 (1945 hom., cov: 33)
• Consequence: EBF3 NM_001375380.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBF3	NM_001375380.1	c.555-23498A>G		intron_variant	Intron 6 of 16	ENST00000440978.2	NP_001362309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBF3	ENST00000440978.2	c.555-23498A>G		intron_variant	Intron 6 of 16	3	NM_001375380.1	ENSP00000387543.2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21217 AN: 152160 Hom.: 1941 Cov.: 33

Gnomad AFR AF: 0.0355

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.0952

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.139 AC: 21241 AN: 152278 Hom.: 1945 Cov.: 33 AF XY: 0.143 AC XY: 10618 AN XY: 74458

African (AFR) AF: 0.0354 AC: 1472 AN: 41582

American (AMR) AF: 0.211 AC: 3222 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0952 AC: 330 AN: 3468

East Asian (EAS) AF: 0.173 AC: 893 AN: 5176

South Asian (SAS) AF: 0.160 AC: 770 AN: 4822

European-Finnish (FIN) AF: 0.228 AC: 2417 AN: 10604

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11745 AN: 68010

Other (OTH) AF: 0.127 AC: 268 AN: 2116

Alfa AF: 0.158 Hom.: 1152

Bravo AF: 0.135

Asia WGS AF: 0.163 AC: 566 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.85
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: rs12771404; hg19: chr10-131699611;