16-67195890-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAG

Variant names:

• chr16-67195890-ACAGCAGCAG-A
• rs3830472
• NM_001950.4:c.950_958delGCAGCAGCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001950.4(E2F4):​c.950_958delGCAGCAGCA​(p.Ser317_Ser319del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00292 in 1,608,046 control chromosomes in the GnomAD database, including 27 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.011 (21 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1593/150436) while in subpopulation AFR AF= 0.0332 (1357/40822). AF 95% confidence interval is 0.0318. There are 21 homozygotes in gnomad4. There are 761 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1593 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F4	NM_001950.4	c.950_958delGCAGCAGCA	p.Ser317_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.950_958delGCAGCAGCA	p.Ser317_Ser319del	disruptive_inframe_deletion	Exon 7 of 10	1	NM_001950.4	ENSP00000368686.3

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1588 AN: 150340 Hom.: 21 Cov.: 31

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00389

Gnomad SAS AF: 0.00293

Gnomad FIN AF: 0.000390

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00145

Gnomad OTH AF: 0.00822

GnomAD4 exome AF: 0.00213 AC: 3099 AN: 1457610 Hom.: 6 AF XY: 0.00210 AC XY: 1522 AN XY: 725030

Gnomad4 AFR exome AF: 0.0325

Gnomad4 AMR exome AF: 0.00271

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00427

Gnomad4 SAS exome AF: 0.00299

Gnomad4 FIN exome AF: 0.000603

Gnomad4 NFE exome AF: 0.00111

Gnomad4 OTH exome AF: 0.00318

GnomAD4 genome AF: 0.0106 AC: 1593 AN: 150436 Hom.: 21 Cov.: 31 AF XY: 0.0104 AC XY: 761 AN XY: 73436

Gnomad4 AFR AF: 0.0332

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00390

Gnomad4 SAS AF: 0.00314

Gnomad4 FIN AF: 0.000390

Gnomad4 NFE AF: 0.00145

Gnomad4 OTH AF: 0.00813

ClinVar

Not reported in ClinVar

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;