8-25852353-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022659.4(EBF2):c.1529-1592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,992 control chromosomes in the GnomAD database, including 6,807 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 0.30 (6807 hom., cov: 32)
• Consequence: EBF2 NM_022659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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]

LOC102723395 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBF2	NM_022659.4	c.1529-1592G>A		intron_variant		ENST00000520164.6
LOC102723395	XR_001745848.2	n.213+2426C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBF2	ENST00000520164.6	c.1529-1592G>A		intron_variant		2	NM_022659.4	P1
EBF2	ENST00000408929.7	c.1085-1592G>A		intron_variant		2
EBF2	ENST00000535548.1	c.*23-1592G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44886 AN: 151878 Hom.: 6799 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.296 AC: 44920 AN: 151992 Hom.: 6807 Cov.: 32 AF XY: 0.296 AC XY: 21986 AN XY: 74262

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.306

Alfa AF: 0.137 Hom.: 252

Bravo AF: 0.297

Asia WGS AF: 0.294 AC: 1025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.0
Dann	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs10503776; hg19: chr8-25709869;