rs3213180

Positions:

• chr20-33675818-G-C
• chr20-33675818-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005225.3(E2F1):​c.*914C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.084 in 185,128 control chromosomes in the GnomAD database, including 967 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 0.080 (749 hom., cov: 32)
  • Exomes 𝑓: 0.10 (218 hom.)
• Consequence: E2F1 NM_005225.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348

Genes affected

E2F1 (HGNC:3113): (E2F transcription factor 1) 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, E2F2 and E2F3, have an additional cyclin binding domain. This protein binds preferentially to retinoblastoma protein pRB in a cell-cycle dependent manner. It can mediate both cell proliferation and p53-dependent/independent apoptosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
E2F1	NM_005225.3	c.*914C>G		3_prime_UTR_variant	7/7	ENST00000343380.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
E2F1	ENST00000343380.6	c.*914C>G		3_prime_UTR_variant	7/7	1	NM_005225.3	P1

Frequencies

GnomAD3 genomes AF: 0.0802 AC: 12190 AN: 152046 Hom.: 749 Cov.: 32

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0930

Gnomad OTH AF: 0.0541

GnomAD4 exome AF: 0.102 AC: 3364 AN: 32964 Hom.: 218 Cov.: 0 AF XY: 0.101 AC XY: 1734 AN XY: 17220

Gnomad4 AFR exome AF: 0.0191

Gnomad4 AMR exome AF: 0.0470

Gnomad4 ASJ exome AF: 0.0784

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0799

Gnomad4 NFE exome AF: 0.0875

Gnomad4 OTH exome AF: 0.0919

GnomAD4 genome AF: 0.0801 AC: 12187 AN: 152164 Hom.: 749 Cov.: 32 AF XY: 0.0819 AC XY: 6090 AN XY: 74350

Gnomad4 AFR AF: 0.0229

Gnomad4 AMR AF: 0.0795

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0970

Gnomad4 NFE AF: 0.0930

Gnomad4 OTH AF: 0.0536

Alfa AF: 0.0439 Hom.: 30

Bravo AF: 0.0757

Asia WGS AF: 0.185 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.9
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3213180; hg19: chr20-32263624;