NM_001949.5:c.393+24613A>G

Variant names:

• chr6-20427238-A-G
• rs942042
• NM_001949.5:c.393+24613A>G

Variant summary

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

The NM_001949.5(E2F3):​c.393+24613A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 152,202 control chromosomes in the GnomAD database, including 56,784 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 0.86 (56784 hom., cov: 33)
• Consequence: E2F3 NM_001949.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F3	NM_001949.5	c.393+24613A>G		intron_variant	Intron 1 of 6	ENST00000346618.8	NP_001940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F3	ENST00000346618.8	c.393+24613A>G		intron_variant	Intron 1 of 6	1	NM_001949.5	ENSP00000262904.4
E2F3	ENST00000535432.2	c.18+23406A>G		intron_variant	Intron 1 of 6	1		ENSP00000443418.1

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130672 AN: 152084 Hom.: 56754 Cov.: 33

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.912

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.887

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

GnomAD4 genome AF: 0.859 AC: 130751 AN: 152202 Hom.: 56784 Cov.: 33 AF XY: 0.858 AC XY: 63808 AN XY: 74392

African (AFR) AF: 0.722 AC: 29938 AN: 41486

American (AMR) AF: 0.912 AC: 13954 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2934 AN: 3470

East Asian (EAS) AF: 0.932 AC: 4822 AN: 5176

South Asian (SAS) AF: 0.925 AC: 4465 AN: 4828

European-Finnish (FIN) AF: 0.842 AC: 8917 AN: 10594

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62724 AN: 68030

Other (OTH) AF: 0.888 AC: 1880 AN: 2116

Alfa AF: 0.908 Hom.: 28194

Bravo AF: 0.859

Asia WGS AF: 0.898 AC: 3125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.46
PhyloP100		-1.6
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: rs942042; hg19: chr6-20427469;