10-129840860-A-G

Variant names:

• chr10-129840860-A-G
• rs372920454
• NM_001375380.1:c.1545T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001375380.1(EBF3):​c.1545T>C​(p.Ala515Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,613,508 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00036 (5 hom.)
• Consequence: EBF3 NM_001375380.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.47
• 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, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 10-129840860-A-G is Benign according to our data. Variant chr10-129840860-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3257656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.47 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000177 (27/152192) while in subpopulation SAS AF = 0.00186 (9/4830). AF 95% confidence interval is 0.000971. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 27 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF3	NM_001375380.1	MANE Select	c.1545T>C	p.Ala515Ala	synonymous	Exon 14 of 17	NP_001362309.1	H0Y3W9
	EBF3	NM_001375379.1		c.1545T>C	p.Ala515Ala	synonymous	Exon 14 of 16	NP_001362308.1	Q9H4W6-1
	EBF3	NM_001375389.1		c.1545T>C	p.Ala515Ala	synonymous	Exon 14 of 17	NP_001362318.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF3	ENST00000440978.2	TSL:3 MANE Select	c.1545T>C	p.Ala515Ala	synonymous	Exon 14 of 17	ENSP00000387543.2	H0Y3W9
	EBF3	ENST00000368648.8	TSL:1	c.1518T>C	p.Ala506Ala	synonymous	Exon 15 of 17	ENSP00000357637.3	Q9H4W6-2
	EBF3	ENST00000904893.1		c.1518T>C	p.Ala506Ala	synonymous	Exon 14 of 17	ENSP00000574952.1

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000594 AC: 149 AN: 250636 AF XY: 0.000842

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000256

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000360 AC: 526 AN: 1461316 Hom.: 5 Cov.: 31 AF XY: 0.000499 AC XY: 363 AN XY: 726928

African (AFR) AF: 0.0000299 AC: 1 AN: 33474

American (AMR) AF: 0.000112 AC: 5 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00394 AC: 340 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.000125 AC: 139 AN: 1111720

Other (OTH) AF: 0.000596 AC: 36 AN: 60374

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152192 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74330

African (AFR) AF: 0.0000724 AC: 3 AN: 41456

American (AMR) AF: 0.000327 AC: 5 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68040

Other (OTH) AF: 0.00144 AC: 3 AN: 2090

Alfa AF: 0.000196 Hom.: 0

Bravo AF: 0.000215

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

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	-0.50
CADD	Benign	8.5
DANN	Benign	0.75
PhyloP100		3.5
Mutation Taster		=100/0	polymorphism

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: rs372920454; hg19: chr10-131639124;