rs3213177

Variant names:

• chr20-33676727-C-A
• rs3213177
• NM_005225.3:c.*5G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-33676727-C-A
• chr20-33676727-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005225.3(E2F1):​c.*5G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,605,244 control chromosomes in the GnomAD database, including 2,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.038 (160 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1854 hom.)
• Consequence: E2F1 NM_005225.3 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.881
• Publications: 8 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 20-33676727-C-A is Benign according to our data. Variant chr20-33676727-C-A is described in ClinVar as Benign. ClinVar VariationId is 3055516.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

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.*5G>T		3_prime_UTR	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.*5G>T		3_prime_UTR	Exon 7 of 7	ENSP00000345571.5	Q01094
	E2F1	ENST00000932104.1		c.*5G>T		3_prime_UTR	Exon 7 of 7	ENSP00000602163.1
	E2F1	ENST00000932103.1		c.*5G>T		3_prime_UTR	Exon 7 of 7	ENSP00000602162.1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5707 AN: 152138 Hom.: 158 Cov.: 32

Gnomad AFR AF: 0.00893

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0459

Gnomad OTH AF: 0.0382

GnomAD2 exomes AF: 0.0510 AC: 12117 AN: 237798 AF XY: 0.0479

Gnomad AFR exome AF: 0.00784

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.0388

Gnomad EAS exome AF: 0.000278

Gnomad FIN exome AF: 0.0468

Gnomad NFE exome AF: 0.0462

Gnomad OTH exome AF: 0.0445

GnomAD4 exome AF: 0.0456 AC: 66270 AN: 1452988 Hom.: 1854 Cov.: 31 AF XY: 0.0448 AC XY: 32360 AN XY: 722076

African (AFR) AF: 0.00729 AC: 243 AN: 33354

American (AMR) AF: 0.125 AC: 5476 AN: 43828

Ashkenazi Jewish (ASJ) AF: 0.0394 AC: 1010 AN: 25608

East Asian (EAS) AF: 0.000734 AC: 29 AN: 39520

South Asian (SAS) AF: 0.0404 AC: 3427 AN: 84766

European-Finnish (FIN) AF: 0.0520 AC: 2714 AN: 52232

Middle Eastern (MID) AF: 0.0201 AC: 115 AN: 5718

European-Non Finnish (NFE) AF: 0.0457 AC: 50634 AN: 1107914

Other (OTH) AF: 0.0437 AC: 2622 AN: 60048

GnomAD4 genome AF: 0.0375 AC: 5712 AN: 152256 Hom.: 160 Cov.: 32 AF XY: 0.0377 AC XY: 2808 AN XY: 74450

African (AFR) AF: 0.00890 AC: 370 AN: 41554

American (AMR) AF: 0.0792 AC: 1212 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0363 AC: 126 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0377 AC: 182 AN: 4822

European-Finnish (FIN) AF: 0.0481 AC: 511 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0459 AC: 3119 AN: 67988

Other (OTH) AF: 0.0378 AC: 80 AN: 2116

Alfa AF: 0.0419 Hom.: 175

Bravo AF: 0.0396

Asia WGS AF: 0.0170 AC: 59 AN: 3478

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	-0.66
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs3213177; hg19: chr20-32264533;