chr1-23511068-C-G

Variant names:

• chr1-23511068-C-G
• rs3218203
• NM_004091.4:c.1046-920G>C

Variant summary

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

The NM_004091.4(E2F2):​c.1046-920G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 151,936 control chromosomes in the GnomAD database, including 2,899 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 0.19 (2899 hom., cov: 31)
• Consequence: E2F2 NM_004091.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933
• Publications: 9 publications found

Genes affected

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F2	NM_004091.4	c.1046-920G>C		intron_variant	Intron 6 of 6	ENST00000361729.3	NP_004082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F2	ENST00000361729.3	c.1046-920G>C		intron_variant	Intron 6 of 6	1	NM_004091.4	ENSP00000355249.2

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28865 AN: 151818 Hom.: 2895 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.0974

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.190 AC: 28898 AN: 151936 Hom.: 2899 Cov.: 31 AF XY: 0.186 AC XY: 13778 AN XY: 74242

African (AFR) AF: 0.235 AC: 9719 AN: 41422

American (AMR) AF: 0.161 AC: 2462 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 449 AN: 3470

East Asian (EAS) AF: 0.0973 AC: 503 AN: 5170

South Asian (SAS) AF: 0.0988 AC: 475 AN: 4810

European-Finnish (FIN) AF: 0.146 AC: 1540 AN: 10556

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13105 AN: 67936

Other (OTH) AF: 0.195 AC: 412 AN: 2110

Alfa AF: 0.0955 Hom.: 129

Bravo AF: 0.195

Asia WGS AF: 0.107 AC: 374 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	1.9
DANN	Benign	0.78
PhyloP100		-0.93
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: rs3218203; hg19: chr1-23837560;