rs10503781

Variant names:

• chr8-26022210-T-C
• rs10503781
• NM_022659.4:c.551+10875A>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.551+10875A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,218 control chromosomes in the GnomAD database, including 1,708 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 0.13 (1708 hom., cov: 33)
• Consequence: EBF2 NM_022659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBF2	NM_022659.4	c.551+10875A>G		intron_variant	Intron 6 of 15	ENST00000520164.6	NP_073150.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBF2	ENST00000520164.6	c.551+10875A>G		intron_variant	Intron 6 of 15	2	NM_022659.4	ENSP00000430241.1
EBF2	ENST00000408929.7	c.107+10875A>G		intron_variant	Intron 5 of 14	2		ENSP00000386178.3

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20100 AN: 152100 Hom.: 1707 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0940

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.132 AC: 20117 AN: 152218 Hom.: 1708 Cov.: 33 AF XY: 0.135 AC XY: 10027 AN XY: 74418

African (AFR) AF: 0.161 AC: 6700 AN: 41524

American (AMR) AF: 0.103 AC: 1575 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3470

East Asian (EAS) AF: 0.426 AC: 2201 AN: 5164

South Asian (SAS) AF: 0.170 AC: 820 AN: 4822

European-Finnish (FIN) AF: 0.154 AC: 1634 AN: 10596

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0941 AC: 6398 AN: 68022

Other (OTH) AF: 0.129 AC: 272 AN: 2114

Alfa AF: 0.109 Hom.: 3401

Bravo AF: 0.130

Asia WGS AF: 0.297 AC: 1034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.64
PhyloP100		-0.99
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: rs10503781; hg19: chr8-25879726;