NM_022659.4:c.1056G>A

Variant names:

• chr8-25862751-C-T
• rs28454030
• NM_022659.4:c.1056G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_022659.4(EBF2):​c.1056G>A​(p.Lys352Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,605,392 control chromosomes in the GnomAD database, including 335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (177 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (158 hom.)
• Consequence: EBF2 NM_022659.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.368
• Publications: 3 publications found

Genes affected

EBF2 (HGNC:19090): (EBF transcription factor 2) The protein encoded by this gene belongs to the COE (Collier/Olf/EBF) family of non-basic, helix-loop-helix transcription factors that have a well conserved DNA binding domain. The COE family proteins play an important role in variety of developmental processes. Studies in mouse suggest that this gene may be involved in the differentiation of osteoblasts. [provided by RefSeq, Oct 2011]

EBF2 Gene-Disease associations (from GenCC):

• endocrine system disorder

  Inheritance: AD Classification: LIMITED Submitted by: Broad Center for Mendelian Genomics

LOC102723395 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 8-25862751-C-T is Benign according to our data. Variant chr8-25862751-C-T is described in ClinVar as Benign. ClinVar VariationId is 772901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.368 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022659.4. 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
	EBF2	NM_022659.4	MANE Select	c.1056G>A	p.Lys352Lys	synonymous	Exon 11 of 16	NP_073150.2	Q9HAK2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBF2	ENST00000520164.6	TSL:2 MANE Select	c.1056G>A	p.Lys352Lys	synonymous	Exon 11 of 16	ENSP00000430241.1	Q9HAK2-1
	EBF2	ENST00000965179.1		c.1056G>A	p.Lys352Lys	synonymous	Exon 11 of 16	ENSP00000635238.1
	EBF2	ENST00000901147.1		c.705G>A	p.Lys235Lys	synonymous	Exon 7 of 12	ENSP00000571206.1

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3823 AN: 152026 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0211

GnomAD2 exomes AF: 0.00677 AC: 1669 AN: 246472 AF XY: 0.00527

Gnomad AFR exome AF: 0.0842

Gnomad AMR exome AF: 0.00572

Gnomad ASJ exome AF: 0.00170

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00126

Gnomad OTH exome AF: 0.00455

GnomAD4 exome AF: 0.00310 AC: 4506 AN: 1453248 Hom.: 158 Cov.: 30 AF XY: 0.00278 AC XY: 2009 AN XY: 723310

African (AFR) AF: 0.0836 AC: 2775 AN: 33200

American (AMR) AF: 0.00657 AC: 286 AN: 43522

Ashkenazi Jewish (ASJ) AF: 0.00127 AC: 33 AN: 25962

East Asian (EAS) AF: 0.00 AC: 0 AN: 39368

South Asian (SAS) AF: 0.000316 AC: 27 AN: 85320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53062

Middle Eastern (MID) AF: 0.0174 AC: 100 AN: 5740

European-Non Finnish (NFE) AF: 0.000783 AC: 867 AN: 1107194

Other (OTH) AF: 0.00698 AC: 418 AN: 59880

GnomAD4 genome AF: 0.0252 AC: 3834 AN: 152144 Hom.: 177 Cov.: 32 AF XY: 0.0246 AC XY: 1828 AN XY: 74382

African (AFR) AF: 0.0851 AC: 3533 AN: 41492

American (AMR) AF: 0.0114 AC: 174 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 67984

Other (OTH) AF: 0.0209 AC: 44 AN: 2106

Alfa AF: 0.0125 Hom.: 55

Bravo AF: 0.0287

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	4.7
DANN	Benign	0.62
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs28454030; hg19: chr8-25720267;