8-25861305-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_022659.4(EBF2):c.1164+4A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00255 in 1,614,200 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (51 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (38 hom.)
• Consequence: EBF2 NM_022659.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.3809
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.07

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 8-25861305-T-C is Benign according to our data. Variant chr8-25861305-T-C is described in ClinVar as [Benign]. Clinvar id is 789762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1998/152324) while in subpopulation AFR AF= 0.0447 (1857/41564). AF 95% confidence interval is 0.043. There are 51 homozygotes in gnomad4. There are 965 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1997 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBF2	NM_022659.4	c.1164+4A>G		splice_donor_region_variant, intron_variant		ENST00000520164.6
LOC102723395	XR_001745848.2	n.214-8674T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBF2	ENST00000520164.6	c.1164+4A>G		splice_donor_region_variant, intron_variant		2	NM_022659.4	P1
EBF2	ENST00000408929.7	c.720+4A>G		splice_donor_region_variant, intron_variant		2
EBF2	ENST00000535548.1	c.357+4A>G		splice_donor_region_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1997 AN: 152206 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0138

GnomAD3 exomes AF: 0.00358 AC: 893 AN: 249488 Hom.: 15 AF XY: 0.00259 AC XY: 350 AN XY: 135352

Gnomad AFR exome AF: 0.0466

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00145 AC: 2117 AN: 1461876 Hom.: 38 Cov.: 32 AF XY: 0.00120 AC XY: 875 AN XY: 727240

Gnomad4 AFR exome AF: 0.0453

Gnomad4 AMR exome AF: 0.00376

Gnomad4 ASJ exome AF: 0.00172

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000129

Gnomad4 OTH exome AF: 0.00373

GnomAD4 genome AF: 0.0131 AC: 1998 AN: 152324 Hom.: 51 Cov.: 32 AF XY: 0.0130 AC XY: 965 AN XY: 74484

Gnomad4 AFR AF: 0.0447

Gnomad4 AMR AF: 0.00628

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00590 Hom.: 13

Bravo AF: 0.0152

Asia WGS AF: 0.00231 AC: 9 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	11
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.38
dbscSNV1_RF	Benign	0.50
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: rs73553903; hg19: chr8-25718821;