rs11135910

Variant names:

• chr8-26034626-C-T
• rs11135910
• NM_022659.4:c.483-1473G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022659.4(EBF2):​c.483-1473G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,238 control chromosomes in the GnomAD database, including 1,492 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 (1492 hom., cov: 33)
• Consequence: EBF2 NM_022659.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 52 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EBF2	NM_022659.4	c.483-1473G>A		intron_variant	Intron 5 of 15	ENST00000520164.6	NP_073150.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EBF2	ENST00000520164.6	c.483-1473G>A		intron_variant	Intron 5 of 15	2	NM_022659.4	ENSP00000430241.1
EBF2	ENST00000517825.1	n.802-1473G>A		intron_variant	Intron 5 of 5	1
EBF2	ENST00000408929.7	c.39-1473G>A		intron_variant	Intron 4 of 14	2		ENSP00000386178.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20364 AN: 152120 Hom.: 1487 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0306

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.134 AC: 20387 AN: 152238 Hom.: 1492 Cov.: 33 AF XY: 0.130 AC XY: 9672 AN XY: 74440

African (AFR) AF: 0.101 AC: 4199 AN: 41528

American (AMR) AF: 0.159 AC: 2440 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3472

East Asian (EAS) AF: 0.0305 AC: 158 AN: 5188

South Asian (SAS) AF: 0.149 AC: 716 AN: 4816

European-Finnish (FIN) AF: 0.0948 AC: 1005 AN: 10600

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10857 AN: 68016

Other (OTH) AF: 0.134 AC: 284 AN: 2112

Alfa AF: 0.150 Hom.: 6217

Bravo AF: 0.137

Asia WGS AF: 0.133 AC: 459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.3
DANN	Benign	0.61
PhyloP100		-0.0060
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: rs11135910; hg19: chr8-25892142;