16-67195890-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant names:

• chr16-67195890-A-ACAGCAG
• rs3830472
• NM_001950.4:c.953_958dupGCAGCA

Variant summary

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

The NM_001950.4(E2F4):​c.953_958dupGCAGCA​(p.Ser318_Ser319dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00184 in 1,607,942 control chromosomes in the GnomAD database, including 9 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0057 (8 hom., cov: 31)
  • Exomes 𝑓: 0.0014 (1 hom.)
• Consequence: E2F4 NM_001950.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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 = 0.00574 (863/150442) while in subpopulation AFR AF= 0.0167 (681/40828). AF 95% confidence interval is 0.0156. There are 8 homozygotes in gnomad4. There are 405 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 863 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F4	NM_001950.4	c.953_958dupGCAGCA	p.Ser318_Ser319dup	disruptive_inframe_insertion	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.953_958dupGCAGCA	p.Ser318_Ser319dup	disruptive_inframe_insertion	Exon 7 of 10	1	NM_001950.4	ENSP00000368686.3

Frequencies

GnomAD3 genomes AF: 0.00574 AC: 863 AN: 150348 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00447

Gnomad SAS AF: 0.00188

Gnomad FIN AF: 0.00312

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00111

Gnomad OTH AF: 0.00676

GnomAD4 exome AF: 0.00144 AC: 2102 AN: 1457500 Hom.: 1 Cov.: 30 AF XY: 0.00140 AC XY: 1018 AN XY: 724990

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.00168

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00491

Gnomad4 SAS exome AF: 0.00140

Gnomad4 FIN exome AF: 0.00409

Gnomad4 NFE exome AF: 0.000747

Gnomad4 OTH exome AF: 0.00235

GnomAD4 genome AF: 0.00574 AC: 863 AN: 150442 Hom.: 8 Cov.: 31 AF XY: 0.00551 AC XY: 405 AN XY: 73438

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.00159

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00448

Gnomad4 SAS AF: 0.00189

Gnomad4 FIN AF: 0.00312

Gnomad4 NFE AF: 0.00111

Gnomad4 OTH AF: 0.00669

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;