10-129840261-G-A

Variant names:

• chr10-129840261-G-A
• rs7092828
• NM_001375380.1:c.1743C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BS1 BS2

The NM_001375380.1(EBF3):​c.1743C>T​(p.Asn581Asn) 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. 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.498
• 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, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP6: Variant 10-129840261-G-A is Benign according to our data. Variant chr10-129840261-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 755545.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.498 with no splicing effect.
• BS1: 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 10 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.1743C>T	p.Asn581Asn	synonymous	Exon 15 of 17	NP_001362309.1	H0Y3W9
	EBF3	NM_001375379.1		c.1743C>T	p.Asn581Asn	synonymous	Exon 15 of 16	NP_001362308.1	Q9H4W6-1
	EBF3	NM_001375389.1		c.1635C>T	p.Asn545Asn	synonymous	Exon 15 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.1743C>T	p.Asn581Asn	synonymous	Exon 15 of 17	ENSP00000387543.2	H0Y3W9
	EBF3	ENST00000368648.8	TSL:1	c.1608C>T	p.Asn536Asn	synonymous	Exon 16 of 17	ENSP00000357637.3	Q9H4W6-2
	EBF3	ENST00000904893.1		c.1716C>T	p.Asn572Asn	synonymous	Exon 15 of 17	ENSP00000574952.1

Frequencies

GnomAD3 genomes AF: 0.0000663 AC: 10 AN: 150916 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.0000961 AC: 19 AN: 197612 AF XY: 0.000123

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 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

African (AFR) AF: 0.0000634 AC: 2 AN: 31548

American (AMR) AF: 0.0000261 AC: 1 AN: 38320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23574

East Asian (EAS) AF: 0.00 AC: 0 AN: 35292

South Asian (SAS) AF: 0.000321 AC: 26 AN: 80968

European-Finnish (FIN) AF: 0.0000226 AC: 1 AN: 44342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5346

European-Non Finnish (NFE) AF: 0.0000770 AC: 82 AN: 1064622

Other (OTH) AF: 0.000126 AC: 7 AN: 55532

GnomAD4 genome AF: 0.0000663 AC: 10 AN: 150916 Hom.: 0 Cov.: 33 AF XY: 0.0000678 AC XY: 5 AN XY: 73734

African (AFR) AF: 0.000121 AC: 5 AN: 41186

American (AMR) AF: 0.000132 AC: 2 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5034

South Asian (SAS) AF: 0.00 AC: 0 AN: 4666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10326

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

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67752

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000773 Hom.: 0

Bravo AF: 0.0000793

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	5.4
DANN	Benign	0.89
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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