8-25844626-C-G

Variant names:

• chr8-25844626-C-G
• rs369189435
• NM_022659.4:c.1711G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_022659.4(EBF2):​c.1711G>C​(p.Val571Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V571I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: EBF2 NM_022659.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41591024).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

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.1711G>C	p.Val571Leu	missense	Exon 16 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.1711G>C	p.Val571Leu	missense	Exon 16 of 16	ENSP00000430241.1	Q9HAK2-1
	EBF2	ENST00000965179.1		c.1645G>C	p.Val549Leu	missense	Exon 16 of 16	ENSP00000635238.1
	EBF2	ENST00000901147.1		c.1360G>C	p.Val454Leu	missense	Exon 12 of 12	ENSP00000571206.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461704 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727156

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111884

Other (OTH) AF: 0.0000166 AC: 1 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T
Eigen	Benign	0.0021
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		5.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.20
Sift	Benign	0.054	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.60
MutPred		0.17		Loss of sheet (P = 0.0457)
MVP		0.78
MPC		0.52
ClinPred		0.90	D
GERP RS		5.8
Varity_R		0.12
gMVP		0.59
Mutation Taster		=75/25	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: rs369189435; hg19: chr8-25702142;