rs3213182

Positions:

• chr20-33675427-A-C

Variant summary

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

The 20-33675427-A-C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 162,480 control chromosomes in the GnomAD database, including 608 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 0.072 (570 hom., cov: 32)
  • Exomes 𝑓: 0.078 (38 hom.)
• Consequence: E2F1 NM_005225.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.229

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
E2F1	NM_005225.3			downstream_gene_variant		ENST00000343380.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
E2F1	ENST00000343380.6			downstream_gene_variant		1	NM_005225.3	P1
	ENST00000606866.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10942 AN: 152010 Hom.: 570 Cov.: 32

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0871

GnomAD4 exome AF: 0.0782 AC: 810 AN: 10352 Hom.: 38 Cov.: 0 AF XY: 0.0805 AC XY: 440 AN XY: 5464

Gnomad4 AFR exome AF: 0.0169

Gnomad4 AMR exome AF: 0.0340

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0303

Gnomad4 FIN exome AF: 0.0601

Gnomad4 NFE exome AF: 0.0953

Gnomad4 OTH exome AF: 0.0927

GnomAD4 genome AF: 0.0719 AC: 10942 AN: 152128 Hom.: 570 Cov.: 32 AF XY: 0.0691 AC XY: 5137 AN XY: 74374

Gnomad4 AFR AF: 0.0183

Gnomad4 AMR AF: 0.0624

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0424

Gnomad4 FIN AF: 0.0625

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0871

Alfa AF: 0.0993 Hom.: 565

Bravo AF: 0.0712

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3213182; hg19: chr20-32263233;