8-25862751-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_022659.4(EBF2):c.1056G>A(p.Lys352=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,605,392 control chromosomes in the GnomAD database, including 335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (177 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (158 hom.)
• Consequence: EBF2 NM_022659.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.368

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 8-25862751-C-T is Benign according to our data. Variant chr8-25862751-C-T is described in ClinVar as [Benign]. Clinvar id is 772901.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.368 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EBF2	NM_022659.4	c.1056G>A	p.Lys352=	synonymous_variant	11/16	ENST00000520164.6
LOC102723395	XR_001745848.2	n.214-7228C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EBF2	ENST00000520164.6	c.1056G>A	p.Lys352=	synonymous_variant	11/16	2	NM_022659.4	P1
EBF2	ENST00000408929.7	c.612G>A	p.Lys204=	synonymous_variant	10/15	2
EBF2	ENST00000535548.1	c.249G>A	p.Lys83=	synonymous_variant	3/9	2

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3823 AN: 152026 Hom.: 176 Cov.: 32

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0211

GnomAD3 exomes AF: 0.00677 AC: 1669 AN: 246472 Hom.: 67 AF XY: 0.00527 AC XY: 706 AN XY: 133998

Gnomad AFR exome AF: 0.0842

Gnomad AMR exome AF: 0.00572

Gnomad ASJ exome AF: 0.00170

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000199

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00126

Gnomad OTH exome AF: 0.00455

GnomAD4 exome AF: 0.00310 AC: 4506 AN: 1453248 Hom.: 158 Cov.: 30 AF XY: 0.00278 AC XY: 2009 AN XY: 723310

Gnomad4 AFR exome AF: 0.0836

Gnomad4 AMR exome AF: 0.00657

Gnomad4 ASJ exome AF: 0.00127

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000316

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000783

Gnomad4 OTH exome AF: 0.00698

GnomAD4 genome AF: 0.0252 AC: 3834 AN: 152144 Hom.: 177 Cov.: 32 AF XY: 0.0246 AC XY: 1828 AN XY: 74382

Gnomad4 AFR AF: 0.0851

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.0209

Alfa AF: 0.0122 Hom.: 44

Bravo AF: 0.0287

Asia WGS AF: 0.00722 AC: 25 AN: 3478

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

May 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	4.7
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28454030; hg19: chr8-25720267;