rs3218148

chr1-23525295-G-Achr1-23525295-G-Cchr1-23525295-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004091.4(E2F2):c.253-807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,732 control chromosomes in the GnomAD database, including 18,142 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 0.44 (18142 hom., cov: 30)
• Consequence: E2F2 NM_004091.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806

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]

LOC101928163 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
E2F2	NM_004091.4	c.253-807C>T		intron_variant		ENST00000361729.3
LOC101928163	NR_110799.1	n.57-1635G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
E2F2	ENST00000361729.3	c.253-807C>T		intron_variant		1	NM_004091.4	P1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67134 AN: 151614 Hom.: 18152 Cov.: 30

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.442 AC: 67118 AN: 151732 Hom.: 18142 Cov.: 30 AF XY: 0.454 AC XY: 33640 AN XY: 74152

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.452

Alfa AF: 0.364 Hom.: 1184

Bravo AF: 0.413

Asia WGS AF: 0.641 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	5.3
Dann	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs3218148; hg19: chr1-23851787; COSMIC: COSV62276341;