rs9942838

Positions:

• chr8-25884533-T-C

Variant summary

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

The NM_022659.4(EBF2):​c.1009+2222A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,016 control chromosomes in the GnomAD database, including 25,986 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 0.55 (25986 hom., cov: 31)
• Consequence: EBF2 NM_022659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBF2	NM_022659.4	c.1009+2222A>G		intron_variant		ENST00000520164.6	NP_073150.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBF2	ENST00000520164.6	c.1009+2222A>G		intron_variant		2	NM_022659.4	ENSP00000430241	P1
EBF2	ENST00000408929.7	c.565+2222A>G		intron_variant		2		ENSP00000386178
EBF2	ENST00000535548.1	c.202+2222A>G		intron_variant		2		ENSP00000437909

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83876 AN: 151898 Hom.: 25933 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.552 AC: 83982 AN: 152016 Hom.: 25986 Cov.: 31 AF XY: 0.546 AC XY: 40590 AN XY: 74276

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.534

Alfa AF: 0.504 Hom.: 4117

Bravo AF: 0.562

Asia WGS AF: 0.398 AC: 1385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.85

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: rs9942838; hg19: chr8-25742049;