16-67195890-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAG

Variant names:

• chr16-67195890-ACAGCAGCAGCAGCAG-A
• rs3830472
• NM_001950.4:c.944_958delGCAGCAGCAGCAGCA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001950.4(E2F4):​c.944_958delGCAGCAGCAGCAGCA​(p.Ser315_Ser319del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000853 in 1,608,078 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0010 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00083 (2 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 155 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F4	NM_001950.4	c.944_958delGCAGCAGCAGCAGCA	p.Ser315_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.944_958delGCAGCAGCAGCAGCA	p.Ser315_Ser319del	disruptive_inframe_deletion	Exon 7 of 10	1	NM_001950.4	ENSP00000368686.3

Frequencies

GnomAD3 genomes AF: 0.00103 AC: 155 AN: 150348 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000393

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.00868

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000666

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000835 AC: 1217 AN: 1457634 Hom.: 2 AF XY: 0.000841 AC XY: 610 AN XY: 725044

Gnomad4 AFR exome AF: 0.000608

Gnomad4 AMR exome AF: 0.000583

Gnomad4 ASJ exome AF: 0.000537

Gnomad4 EAS exome AF: 0.000683

Gnomad4 SAS exome AF: 0.000362

Gnomad4 FIN exome AF: 0.0106

Gnomad4 NFE exome AF: 0.000434

Gnomad4 OTH exome AF: 0.000932

GnomAD4 genome AF: 0.00103 AC: 155 AN: 150444 Hom.: 1 Cov.: 31 AF XY: 0.00106 AC XY: 78 AN XY: 73440

Gnomad4 AFR AF: 0.000392

Gnomad4 AMR AF: 0.0000661

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.000419

Gnomad4 FIN AF: 0.00868

Gnomad4 NFE AF: 0.000666

Gnomad4 OTH AF: 0.00

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;