16-67195890-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant names:

• chr16-67195890-A-ACAG
• rs3830472
• NM_001950.4:c.956_958dupGCA

Variant summary

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

The NM_001950.4(E2F4):​c.956_958dupGCA​(p.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 0.0292 in 1,607,940 control chromosomes in the GnomAD database, including 161 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.036 (102 hom., cov: 31)
  • Exomes 𝑓: 0.029 (59 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.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F4	NM_001950.4	c.956_958dupGCA	p.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.956_958dupGCA	p.Ser319dup	disruptive_inframe_insertion	Exon 7 of 10	1	NM_001950.4	ENSP00000368686.3

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5384 AN: 150332 Hom.: 102 Cov.: 31

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.0297

Gnomad SAS AF: 0.00941

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0357

GnomAD4 exome AF: 0.0285 AC: 41583 AN: 1457512 Hom.: 59 Cov.: 30 AF XY: 0.0278 AC XY: 20154 AN XY: 724972

Gnomad4 AFR exome AF: 0.0403

Gnomad4 AMR exome AF: 0.0569

Gnomad4 ASJ exome AF: 0.0133

Gnomad4 EAS exome AF: 0.0252

Gnomad4 SAS exome AF: 0.00649

Gnomad4 FIN exome AF: 0.0488

Gnomad4 NFE exome AF: 0.0284

Gnomad4 OTH exome AF: 0.0269

GnomAD4 genome AF: 0.0358 AC: 5390 AN: 150428 Hom.: 102 Cov.: 31 AF XY: 0.0374 AC XY: 2747 AN XY: 73430

Gnomad4 AFR AF: 0.0382

Gnomad4 AMR AF: 0.0584

Gnomad4 ASJ AF: 0.0136

Gnomad4 EAS AF: 0.0300

Gnomad4 SAS AF: 0.00901

Gnomad4 FIN AF: 0.0507

Gnomad4 NFE AF: 0.0309

Gnomad4 OTH AF: 0.0354

Bravo AF: 0.0361

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;