rs4134945

Variant names:

• chr6-20483372-C-T
• rs4134945
• NM_001949.5:c.884+452C>T

Variant summary

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

The NM_001949.5(E2F3):​c.884+452C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0923 in 152,162 control chromosomes in the GnomAD database, including 836 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 0.092 (836 hom., cov: 32)
• Consequence: E2F3 NM_001949.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F3	NM_001949.5	c.884+452C>T		intron_variant	Intron 4 of 6	ENST00000346618.8	NP_001940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F3	ENST00000346618.8	c.884+452C>T		intron_variant	Intron 4 of 6	1	NM_001949.5	ENSP00000262904.4
E2F3	ENST00000535432.2	c.491+452C>T		intron_variant	Intron 4 of 6	1		ENSP00000443418.1

Frequencies

GnomAD3 genomes AF: 0.0924 AC: 14046 AN: 152044 Hom.: 837 Cov.: 32

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.0878

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.0923 AC: 14039 AN: 152162 Hom.: 836 Cov.: 32 AF XY: 0.0931 AC XY: 6926 AN XY: 74370

Gnomad4 AFR AF: 0.0239

Gnomad4 AMR AF: 0.0877

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.115

Alfa AF: 0.125 Hom.: 797

Bravo AF: 0.0862

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.4
DANN	Benign	0.70

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: rs4134945; hg19: chr6-20483603;