rs2328524

chr6-20488003-G-Achr6-20488003-G-Cchr6-20488003-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001949.5(E2F3):c.1000-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,484,722 control chromosomes in the GnomAD database, including 115,515 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 0.33 (9436 hom., cov: 33)
  • Exomes 𝑓: 0.39 (106079 hom.)
• Consequence: E2F3 NM_001949.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.315

Genes affected

E2F3 (HGNC:3115): (E2F transcription factor 3) This gene encodes a member of a small family of transcription factors that function through binding of DP interaction partner proteins. The encoded protein recognizes a specific sequence motif in DNA and interacts directly with the retinoblastoma protein (pRB) to regulate the expression of genes involved in the cell cycle. Altered copy number and activity of this gene have been observed in a number of human cancers. There are pseudogenes for this gene on chromosomes 2 and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
E2F3	NM_001949.5	c.1000-110G>A		intron_variant		ENST00000346618.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
E2F3	ENST00000346618.8	c.1000-110G>A		intron_variant		1	NM_001949.5
E2F3	ENST00000535432.2	c.607-110G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50410 AN: 151978 Hom.: 9432 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.357

GnomAD4 exome AF: 0.392 AC: 522278 AN: 1332626 Hom.: 106079 AF XY: 0.398 AC XY: 265552 AN XY: 666590

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.420

Gnomad4 EAS exome AF: 0.592

Gnomad4 SAS exome AF: 0.565

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.392

GnomAD4 genome AF: 0.331 AC: 50411 AN: 152096 Hom.: 9436 Cov.: 33 AF XY: 0.340 AC XY: 25310 AN XY: 74340

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.356

Alfa AF: 0.385 Hom.: 15524

Bravo AF: 0.317

Asia WGS AF: 0.506 AC: 1761 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	2.4
Dann	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs2328524; hg19: chr6-20488234;