16-67195890-ACAGCAG-A

Position:

• chr16-67195890-ACAGCAG-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001950.4(E2F4):​c.953_958del​(p.Ser318_Ser319del) variant causes a 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 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.77

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]

ACMG classification

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/exons	MANE	UniProt
E2F4	NM_001950.4	c.953_958del	p.Ser318_Ser319del	inframe_deletion	7/10	ENST00000379378.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
E2F4	ENST00000379378.8	c.953_958del	p.Ser318_Ser319del	inframe_deletion	7/10	1	NM_001950.4	P1

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 399 AN: 150346 Hom.: 2 Cov.: 31

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.: 2 AF XY: 0.00272 AC XY: 1968 AN XY: 724714

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.: 2 Cov.: 31 AF XY: 0.00266 AC XY: 195 AN XY: 73438

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

E2F4: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3830472; hg19: chr16-67229793;