Genetic Variant ENSG00000307540:n.203+4294C>A (chr1-23531364-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000826972.1(ENSG00000307540):n.203+4294C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.057 ( 218 hom., cov: 9)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000307540
ENST00000826972.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

Publications

5 publications found

Variant links:

Genes affected

ENSG00000307540 (HGNC:):

ENSG00000307540 links:

E2F2 (HGNC:3114): (E2F transcription factor 2) The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F1 and E2F3, have an additional cyclin binding domain. This protein binds specifically to retinoblastoma protein pRB in a cell-cycle dependent manner, and it exhibits overall 46% amino acid identity to E2F1. [provided by RefSeq, Jul 2008]

E2F2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F2	NM_004091.4 link	c.-571G>T		upstream_gene_variant		ENST00000361729.3	NP_004082.1	Q14209

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000307540	ENST00000826972.1 link	n.203+4294C>A		intron_variant	Intron 2 of 2
E2F2	ENST00000361729.3 link	c.-571G>T		upstream_gene_variant		1	NM_004091.4	ENSP00000355249.2		Q14209

Frequencies

GnomAD3 genomes

AF:

0.0572

AC:

1684

AN:

29420

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00819

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0437

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.0266

Gnomad MID

AF:

0.0281

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.0469

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0569

AC:

1676

AN:

29470

Hom.:

218

Cov.:

AF XY:

0.0484

AC XY:

779

AN XY:

16100

show subpopulations

African (AFR)

AF:

0.00805

AC:

AN:

10804

American (AMR)

AF:

0.0434

AC:

246

AN:

5670

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

AN:

386

East Asian (EAS)

AF:

0.00

AC:

AN:

858

South Asian (SAS)

AF:

0.201

AC:

112

AN:

558

European-Finnish (FIN)

AF:

0.0266

AC:

AN:

3234

Middle Eastern (MID)

AF:

0.0321

AC:

AN:

156

European-Non Finnish (NFE)

AF:

0.142

AC:

1038

AN:

7310

Other (OTH)

AF:

0.0455

AC:

AN:

440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.631

Heterozygous variant carriers

134

179

224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0182

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

1.8

PromoterAI

0.088

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over