rs3213141

Variant names:

• chr20-33686574-G-A
• rs3213141
• NM_005225.3:c.-310C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005225.3(E2F1):​c.-310C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,600 control chromosomes in the GnomAD database, including 4,245 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 0.23 (4245 hom., cov: 31)
• Consequence: E2F1 NM_005225.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F1	NM_005225.3	c.-310C>T		upstream_gene_variant		ENST00000343380.6	NP_005216.1
E2F1	XM_047439961.1	c.-310C>T		upstream_gene_variant			XP_047295917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F1	ENST00000343380.6	c.-310C>T		upstream_gene_variant		1	NM_005225.3	ENSP00000345571.5

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35190 AN: 151494 Hom.: 4247 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.232 AC: 35196 AN: 151600 Hom.: 4245 Cov.: 31 AF XY: 0.232 AC XY: 17146 AN XY: 74044

African (AFR) AF: 0.200 AC: 8275 AN: 41436

American (AMR) AF: 0.187 AC: 2857 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 879 AN: 3452

East Asian (EAS) AF: 0.319 AC: 1618 AN: 5078

South Asian (SAS) AF: 0.218 AC: 1054 AN: 4824

European-Finnish (FIN) AF: 0.261 AC: 2755 AN: 10556

Middle Eastern (MID) AF: 0.266 AC: 77 AN: 290

European-Non Finnish (NFE) AF: 0.251 AC: 16987 AN: 67682

Other (OTH) AF: 0.229 AC: 481 AN: 2102

Alfa AF: 0.242 Hom.: 533

Bravo AF: 0.227

Asia WGS AF: 0.240 AC: 826 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Uncertain	0.98
PhyloP100		1.6
PromoterAI		0.040	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3213141; hg19: chr20-32274380;