NM_005225.3:c.1245C>T

Variant names:

• chr20-33676801-G-A
• rs147013405
• NM_005225.3:c.1245C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_005225.3(E2F1):​c.1245C>T​(p.Leu415Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00046 in 1,603,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (0 hom.)
• Consequence: E2F1 NM_005225.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.558
• Publications: 5 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=-0.65).
• BP6: Variant 20-33676801-G-A is Benign according to our data. Variant chr20-33676801-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3050503.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.558 with no splicing effect.
• BS2: High AC in GnomAd4 at 75 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005225.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F1	NM_005225.3	MANE Select	c.1245C>T	p.Leu415Leu	synonymous	Exon 7 of 7	NP_005216.1	Q01094

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F1	ENST00000343380.6	TSL:1 MANE Select	c.1245C>T	p.Leu415Leu	synonymous	Exon 7 of 7	ENSP00000345571.5	Q01094
	E2F1	ENST00000932104.1		c.1272C>T	p.Leu424Leu	synonymous	Exon 7 of 7	ENSP00000602163.1
	E2F1	ENST00000932103.1		c.1236C>T	p.Leu412Leu	synonymous	Exon 7 of 7	ENSP00000602162.1

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000518 AC: 119 AN: 229646 AF XY: 0.000570

Gnomad AFR exome AF: 0.000210

Gnomad AMR exome AF: 0.00146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000501

Gnomad NFE exome AF: 0.000480

Gnomad OTH exome AF: 0.00106

GnomAD4 exome AF: 0.000457 AC: 663 AN: 1451008 Hom.: 0 Cov.: 31 AF XY: 0.000459 AC XY: 331 AN XY: 720832

African (AFR) AF: 0.000271 AC: 9 AN: 33178

American (AMR) AF: 0.00131 AC: 57 AN: 43556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25882

East Asian (EAS) AF: 0.00 AC: 0 AN: 39004

South Asian (SAS) AF: 0.000379 AC: 32 AN: 84472

European-Finnish (FIN) AF: 0.0000380 AC: 2 AN: 52564

Middle Eastern (MID) AF: 0.00261 AC: 15 AN: 5752

European-Non Finnish (NFE) AF: 0.000475 AC: 526 AN: 1106648

Other (OTH) AF: 0.000367 AC: 22 AN: 59952

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32 AN XY: 74448

African (AFR) AF: 0.000241 AC: 10 AN: 41554

American (AMR) AF: 0.00157 AC: 24 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68018

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.000507 Hom.: 0

Bravo AF: 0.000457

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	E2F1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	2.9
DANN	Benign	0.81
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism

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: rs147013405; hg19: chr20-32264607; COSMIC: COSV99865360; COSMIC: COSV99865360;