rs3218148

Variant names:

• chr1-23525295-G-A
• rs3218148
• NM_004091.4:c.253-807C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-23525295-G-A
• chr1-23525295-G-C
• chr1-23525295-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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]

ENSG00000307540 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004091.4. 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.253-807C>T		intron	N/A	NP_004082.1	Q14209
	LOC101928163	NR_110799.1		n.57-1635G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F2	ENST00000361729.3	TSL:1 MANE Select	c.253-807C>T		intron	N/A	ENSP00000355249.2	Q14209
	E2F2	ENST00000915331.1		c.253-807C>T		intron	N/A	ENSP00000585390.1
	ENSG00000307540	ENST00000826972.1		n.63-1635G>A		intron	N/A

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

African (AFR) AF: 0.128 AC: 5281 AN: 41364

American (AMR) AF: 0.448 AC: 6828 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1824 AN: 3470

East Asian (EAS) AF: 0.828 AC: 4235 AN: 5114

South Asian (SAS) AF: 0.639 AC: 3072 AN: 4808

European-Finnish (FIN) AF: 0.671 AC: 7073 AN: 10540

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37170 AN: 67878

Other (OTH) AF: 0.452 AC: 951 AN: 2104

Alfa AF: 0.350 Hom.: 1193

Bravo AF: 0.413

Asia WGS AF: 0.641 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.3
DANN	Benign	0.91
PhyloP100		-0.81
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: rs3218148; hg19: chr1-23851787; COSMIC: COSV62276341;