1-23531364-C-G

Variant names:

• chr1-23531364-C-G
• rs3218123
• ENST00000826972.1:n.203+4294C>G

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>G 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 0.000034 (0 hom., cov: 9)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000307540 ENST00000826972.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 5 publications found

Genes affected

ENSG00000307540 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000826972.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F2	NM_004091.4	MANE Select	c.-571G>C		upstream_gene	N/A	NP_004082.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000307540	ENST00000826972.1		n.203+4294C>G		intron	N/A
	E2F2	ENST00000361729.3	TSL:1 MANE Select	c.-571G>C		upstream_gene	N/A	ENSP00000355249.2
	E2F2	ENST00000915331.1		c.-571G>C		upstream_gene	N/A	ENSP00000585390.1

Frequencies

GnomAD3 genomes AF: 0.0000340 AC: 1 AN: 29438 Hom.: 0 Cov.: 9

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00179

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000340 AC: 1 AN: 29438 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 16050

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 10746

American (AMR) AF: 0.00 AC: 0 AN: 5658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 388

East Asian (EAS) AF: 0.00 AC: 0 AN: 864

South Asian (SAS) AF: 0.00179 AC: 1 AN: 560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 178

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 7330

Other (OTH) AF: 0.00 AC: 0 AN: 426

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.77
PhyloP100		1.8
PromoterAI		-0.010	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3218123; hg19: chr1-23857856;