rs142009843

Variant names:

• chr20-33676870-G-A
• rs142009843
• NM_005225.3:c.1176C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-33676870-G-A
• chr20-33676870-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005225.3(E2F1):​c.1176C>T​(p.Ser392Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000607 in 1,582,378 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (2 hom.)
• Consequence: E2F1 NM_005225.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.49
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 20-33676870-G-A is Benign according to our data. Variant chr20-33676870-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3033085.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.49 with no splicing effect.
• BS2: High AC in GnomAd4 at 65 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.1176C>T	p.Ser392Ser	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.1176C>T	p.Ser392Ser	synonymous	Exon 7 of 7	ENSP00000345571.5	Q01094
	E2F1	ENST00000932104.1		c.1203C>T	p.Ser401Ser	synonymous	Exon 7 of 7	ENSP00000602163.1
	E2F1	ENST00000932103.1		c.1167C>T	p.Ser389Ser	synonymous	Exon 7 of 7	ENSP00000602162.1

Frequencies

GnomAD3 genomes AF: 0.000427 AC: 65 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000499 AC: 98 AN: 196498 AF XY: 0.000527

Gnomad AFR exome AF: 0.000265

Gnomad AMR exome AF: 0.000536

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000684

Gnomad FIN exome AF: 0.000172

Gnomad NFE exome AF: 0.000889

Gnomad OTH exome AF: 0.000195

GnomAD4 exome AF: 0.000626 AC: 895 AN: 1430052 Hom.: 2 Cov.: 32 AF XY: 0.000591 AC XY: 419 AN XY: 708746

African (AFR) AF: 0.0000307 AC: 1 AN: 32524

American (AMR) AF: 0.000390 AC: 16 AN: 41014

Ashkenazi Jewish (ASJ) AF: 0.0000391 AC: 1 AN: 25544

East Asian (EAS) AF: 0.00 AC: 0 AN: 37660

South Asian (SAS) AF: 0.00 AC: 0 AN: 82444

European-Finnish (FIN) AF: 0.000255 AC: 13 AN: 50956

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5724

European-Non Finnish (NFE) AF: 0.000771 AC: 844 AN: 1095142

Other (OTH) AF: 0.000322 AC: 19 AN: 59044

GnomAD4 genome AF: 0.000427 AC: 65 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30 AN XY: 74496

African (AFR) AF: 0.0000722 AC: 3 AN: 41572

American (AMR) AF: 0.000196 AC: 3 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10628

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

European-Non Finnish (NFE) AF: 0.000794 AC: 54 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000579 Hom.: 0

Bravo AF: 0.000419

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	E2F1-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.0
DANN	Benign	0.87
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs142009843; hg19: chr20-32264676;