6-20467132-A-G

Variant names:

• chr6-20467132-A-G
• rs2328523
• NM_001949.5:c.394-12714A>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.394-12714A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,134 control chromosomes in the GnomAD database, including 48,033 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 0.79 (48033 hom., cov: 32)
• Consequence: E2F3 NM_001949.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001949.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F3	NM_001949.5	MANE Select	c.394-12714A>G		intron	N/A	NP_001940.1
	E2F3	NM_001243076.3		c.19-12714A>G		intron	N/A	NP_001230005.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F3	ENST00000346618.8	TSL:1 MANE Select	c.394-12714A>G		intron	N/A	ENSP00000262904.4
	E2F3	ENST00000535432.2	TSL:1	c.19-12714A>G		intron	N/A	ENSP00000443418.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120353 AN: 152016 Hom.: 47997 Cov.: 32

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.792 AC: 120449 AN: 152134 Hom.: 48033 Cov.: 32 AF XY: 0.787 AC XY: 58532 AN XY: 74358

African (AFR) AF: 0.868 AC: 36019 AN: 41500

American (AMR) AF: 0.753 AC: 11522 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2322 AN: 3470

East Asian (EAS) AF: 0.597 AC: 3081 AN: 5158

South Asian (SAS) AF: 0.767 AC: 3697 AN: 4822

European-Finnish (FIN) AF: 0.735 AC: 7782 AN: 10582

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53389 AN: 67992

Other (OTH) AF: 0.771 AC: 1627 AN: 2110

Alfa AF: 0.783 Hom.: 19220

Bravo AF: 0.796

Asia WGS AF: 0.721 AC: 2510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.8
DANN	Benign	0.36
PhyloP100		-0.28
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: rs2328523; hg19: chr6-20467363;