rs9942838

Variant names:

• chr8-25884533-T-C
• rs9942838
• NM_022659.4:c.1009+2222A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EBF2	NM_022659.4	c.1009+2222A>G		intron_variant	Intron 10 of 15	ENST00000520164.6	NP_073150.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBF2	ENST00000520164.6	c.1009+2222A>G		intron_variant	Intron 10 of 15	2	NM_022659.4	ENSP00000430241.1
EBF2	ENST00000408929.7	c.565+2222A>G		intron_variant	Intron 9 of 14	2		ENSP00000386178.3
EBF2	ENST00000535548.1	c.202+2222A>G		intron_variant	Intron 2 of 8	2		ENSP00000437909.1

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

African (AFR) AF: 0.835 AC: 34637 AN: 41490

American (AMR) AF: 0.413 AC: 6308 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1991 AN: 3462

East Asian (EAS) AF: 0.208 AC: 1073 AN: 5158

South Asian (SAS) AF: 0.552 AC: 2654 AN: 4812

European-Finnish (FIN) AF: 0.423 AC: 4466 AN: 10568

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31225 AN: 67952

Other (OTH) AF: 0.534 AC: 1123 AN: 2104

Alfa AF: 0.512 Hom.: 4387

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
PhyloP100		0.024
Mutation Taster		=100/0	polymorphism (auto)

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: rs9942838; hg19: chr8-25742049;