rs2071054

Positions:

• chr20-33678033-A-G
• chr20-33678033-A-T

Variant summary

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

The NM_005225.3(E2F1):​c.725+168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,140 control chromosomes in the GnomAD database, including 14,821 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 0.42 (14821 hom., cov: 33)
• Consequence: E2F1 NM_005225.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.538

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
E2F1	NM_005225.3	c.725+168T>C		intron_variant		ENST00000343380.6
E2F1	XM_047439961.1	c.725+168T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
E2F1	ENST00000343380.6	c.725+168T>C		intron_variant		1	NM_005225.3	P1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63140 AN: 152022 Hom.: 14800 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.415 AC: 63197 AN: 152140 Hom.: 14821 Cov.: 33 AF XY: 0.415 AC XY: 30891 AN XY: 74380

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.396

Alfa AF: 0.313 Hom.: 7452

Bravo AF: 0.434

Asia WGS AF: 0.342 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.55

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: rs2071054; hg19: chr20-32265839;