16-67195890-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant names:

• chr16-67195890-ACAG-A
• rs3830472
• NM_001950.4:c.956_958delGCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001950.4(E2F4):​c.956_958delGCA​(p.Ser319del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0226 in 1,250,328 control chromosomes in the GnomAD database, including 8 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0036 (2 hom., cov: 31)
  • Exomes 𝑓: 0.025 (6 hom.)
• Consequence: E2F4 NM_001950.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F4	NM_001950.4	c.956_958delGCA	p.Ser319del	disruptive_inframe_deletion	Exon 7 of 10	ENST00000379378.8	NP_001941.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F4	ENST00000379378.8	c.956_958delGCA	p.Ser319del	disruptive_inframe_deletion	Exon 7 of 10	1	NM_001950.4	ENSP00000368686.3

Frequencies

GnomAD3 genomes AF: 0.00364 AC: 546 AN: 149944 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00359

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00145

Gnomad EAS AF: 0.00253

Gnomad SAS AF: 0.00376

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00406

Gnomad OTH AF: 0.00290

GnomAD4 exome AF: 0.0252 AC: 27764 AN: 1100290 Hom.: 6 AF XY: 0.0276 AC XY: 14611 AN XY: 529010

Gnomad4 AFR exome AF: 0.0243

Gnomad4 AMR exome AF: 0.0591

Gnomad4 ASJ exome AF: 0.0414

Gnomad4 EAS exome AF: 0.0686

Gnomad4 SAS exome AF: 0.0593

Gnomad4 FIN exome AF: 0.0502

Gnomad4 NFE exome AF: 0.0205

Gnomad4 OTH exome AF: 0.0302

GnomAD4 genome AF: 0.00365 AC: 547 AN: 150038 Hom.: 2 Cov.: 31 AF XY: 0.00377 AC XY: 276 AN XY: 73228

Gnomad4 AFR AF: 0.00363

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.00145

Gnomad4 EAS AF: 0.00254

Gnomad4 SAS AF: 0.00377

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.00405

Gnomad4 OTH AF: 0.00287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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;