NM_001949.5:c.393+15473C>T

Variant names:

• chr6-20418098-C-T
• rs2328488
• NM_001949.5:c.393+15473C>T

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+15473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,126 control chromosomes in the GnomAD database, including 3,955 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 0.21 (3955 hom., cov: 32)
• Consequence: E2F3 NM_001949.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F3	NM_001949.5	c.393+15473C>T		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+15473C>T		intron_variant	Intron 1 of 6	1	NM_001949.5	ENSP00000262904.4
E2F3	ENST00000535432.2	c.18+14266C>T		intron_variant	Intron 1 of 6	1		ENSP00000443418.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31631 AN: 152008 Hom.: 3955 Cov.: 32

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.208 AC: 31638 AN: 152126 Hom.: 3955 Cov.: 32 AF XY: 0.211 AC XY: 15655 AN XY: 74358

African (AFR) AF: 0.0641 AC: 2662 AN: 41530

American (AMR) AF: 0.237 AC: 3622 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 948 AN: 3472

East Asian (EAS) AF: 0.224 AC: 1160 AN: 5176

South Asian (SAS) AF: 0.314 AC: 1509 AN: 4810

European-Finnish (FIN) AF: 0.268 AC: 2834 AN: 10560

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18035 AN: 67974

Other (OTH) AF: 0.237 AC: 500 AN: 2114

Alfa AF: 0.243 Hom.: 16078

Bravo AF: 0.200

Asia WGS AF: 0.262 AC: 913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.64
PhyloP100		0.30
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: rs2328488; hg19: chr6-20418329;