chr20-33677525-C-T

Variant names:

• chr20-33677525-C-T
• rs35807460
• NM_005225.3:c.741G>A

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.741G>A​(p.Thr247Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000905 in 1,613,974 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0045 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (5 hom.)
• Consequence: E2F1 NM_005225.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.394
• Publications: 1 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=-0.52).
• BP6: Variant 20-33677525-C-T is Benign according to our data. Variant chr20-33677525-C-T is described in ClinVar as Benign. ClinVar VariationId is 3037820.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.394 with no splicing effect.
• BS2: High AC in GnomAd4 at 690 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.741G>A	p.Thr247Thr	synonymous	Exon 5 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.741G>A	p.Thr247Thr	synonymous	Exon 5 of 7	ENSP00000345571.5	Q01094
	E2F1	ENST00000932104.1		c.741G>A	p.Thr247Thr	synonymous	Exon 5 of 7	ENSP00000602163.1
	E2F1	ENST00000932103.1		c.741G>A	p.Thr247Thr	synonymous	Exon 5 of 7	ENSP00000602162.1

Frequencies

GnomAD3 genomes AF: 0.00453 AC: 689 AN: 152154 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00119 AC: 300 AN: 251140 AF XY: 0.000943

Gnomad AFR exome AF: 0.0148

Gnomad AMR exome AF: 0.000869

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000527 AC: 770 AN: 1461702 Hom.: 5 Cov.: 33 AF XY: 0.000454 AC XY: 330 AN XY: 727156

African (AFR) AF: 0.0153 AC: 512 AN: 33478

American (AMR) AF: 0.000873 AC: 39 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00176 AC: 46 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.0000791 AC: 88 AN: 1111906

Other (OTH) AF: 0.00123 AC: 74 AN: 60386

GnomAD4 genome AF: 0.00453 AC: 690 AN: 152272 Hom.: 4 Cov.: 32 AF XY: 0.00427 AC XY: 318 AN XY: 74456

African (AFR) AF: 0.0154 AC: 640 AN: 41548

American (AMR) AF: 0.00157 AC: 24 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68014

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00204 Hom.: 2

Bravo AF: 0.00514

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.52
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs35807460; hg19: chr20-32265331; COSMIC: COSV55778966; COSMIC: COSV55778966;