Variant 16-67195890-ACAGCAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001950.4(E2F4):c.953_958delGCAGCA(p.Ser318_Ser319del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00266 in 1,607,448 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0027 ( 2 hom. )

Consequence

E2F4
NM_001950.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.77

Variant links:

Genes affected

E2F4 (HGNC:3118): (E2F transcription factor 4) 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 binds to all three of the tumor suppressor proteins pRB, p107 and p130, but with higher affinity to the last two. It plays an important role in the suppression of proliferation-associated genes, and its gene mutation and increased expression may be associated with human cancer. [provided by RefSeq, Jul 2008]

E2F4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 16-67195890-ACAGCAG-A is Benign according to our data. Variant chr16-67195890-ACAGCAG-A is described in ClinVar as [Benign]. Clinvar id is 2646614.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 399 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F4	NM_001950.4 link	c.953_958delGCAGCA	p.Ser318_Ser319del	disruptive_inframe_deletion	Exon 7 of 10	ENST00000379378.8	NP_001941.2	Q16254

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F4	ENST00000379378.8 link	c.953_958delGCAGCA	p.Ser318_Ser319del	disruptive_inframe_deletion	Exon 7 of 10	1	NM_001950.4	ENSP00000368686.3		Q16254

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

399

AN:

150346

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00536

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.000972

Gnomad SAS

AF:

0.00355

Gnomad FIN

AF:

0.0000975

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00255

Gnomad OTH

AF:

0.00435

GnomAD4 exome

AF:

0.00266

AC:

3877

AN:

1457006

Hom.:

AF XY:

0.00272

AC XY:

1968

AN XY:

724714

show subpopulations

Gnomad4 AFR exome

AF:

0.00271

Gnomad4 AMR exome

AF:

0.00278

Gnomad4 ASJ exome

AF:

0.000537

Gnomad4 EAS exome

AF:

0.000886

Gnomad4 SAS exome

AF:

0.00356

Gnomad4 FIN exome

AF:

0.000189

Gnomad4 NFE exome

AF:

0.00280

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.00265

AC:

399

AN:

150442

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

195

AN XY:

73438

show subpopulations

Gnomad4 AFR

AF:

0.00269

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.000974

Gnomad4 SAS

AF:

0.00356

Gnomad4 FIN

AF:

0.0000975

Gnomad4 NFE

AF:

0.00255

Gnomad4 OTH

AF:

0.00430

Bravo

AF:

0.00276

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

E2F4: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over