1-23530036-C-T

Variant names:

• chr1-23530036-C-T
• rs3218127
• NM_004091.4:c.252+506G>A

Variant summary

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

The NM_004091.4(E2F2):​c.252+506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 152,232 control chromosomes in the GnomAD database, including 324 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 0.056 (324 hom., cov: 32)
• Consequence: E2F2 NM_004091.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F2	NM_004091.4	c.252+506G>A		intron_variant	Intron 1 of 6	ENST00000361729.3	NP_004082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F2	ENST00000361729.3	c.252+506G>A		intron_variant	Intron 1 of 6	1	NM_004091.4	ENSP00000355249.2
ENSG00000307540	ENST00000826972.1	n.203+2966C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8587 AN: 152114 Hom.: 323 Cov.: 32

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0581

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.0578

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

GnomAD4 genome AF: 0.0565 AC: 8599 AN: 152232 Hom.: 324 Cov.: 32 AF XY: 0.0557 AC XY: 4146 AN XY: 74434

African (AFR) AF: 0.0238 AC: 990 AN: 41544

American (AMR) AF: 0.0404 AC: 618 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.120 AC: 577 AN: 4822

European-Finnish (FIN) AF: 0.0581 AC: 616 AN: 10596

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0760 AC: 5165 AN: 68002

Other (OTH) AF: 0.0572 AC: 121 AN: 2116

Alfa AF: 0.0604 Hom.: 39

Bravo AF: 0.0532

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.0
DANN	Benign	0.52
PhyloP100		-0.17
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: rs3218127; hg19: chr1-23856528;