16-67195890-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant names:

• chr16-67195890-A-ACAGCAGCAG
• rs3830472
• NM_001950.4:c.950_958dupGCAGCAGCA

Variant summary

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

The NM_001950.4(E2F4):​c.950_958dupGCAGCAGCA​(p.Ser317_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 0.00465 in 1,607,948 control chromosomes in the GnomAD database, including 106 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (100 hom., cov: 31)
  • Exomes 𝑓: 0.0032 (6 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 (AFR) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F4	NM_001950.4	c.950_958dupGCAGCAGCA	p.Ser317_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.950_958dupGCAGCAGCA	p.Ser317_Ser319dup	disruptive_inframe_insertion	Exon 7 of 10	1	NM_001950.4	ENSP00000368686.3

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2875 AN: 150322 Hom.: 99 Cov.: 31

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.0126

Gnomad SAS AF: 0.00418

Gnomad FIN AF: 0.000292

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00124

Gnomad OTH AF: 0.0150

GnomAD4 exome AF: 0.00315 AC: 4595 AN: 1457530 Hom.: 6 Cov.: 30 AF XY: 0.00300 AC XY: 2176 AN XY: 724980

Gnomad4 AFR exome AF: 0.0636

Gnomad4 AMR exome AF: 0.00655

Gnomad4 ASJ exome AF: 0.00330

Gnomad4 EAS exome AF: 0.00906

Gnomad4 SAS exome AF: 0.00334

Gnomad4 FIN exome AF: 0.000132

Gnomad4 NFE exome AF: 0.000962

Gnomad4 OTH exome AF: 0.00589

GnomAD4 genome AF: 0.0192 AC: 2888 AN: 150418 Hom.: 100 Cov.: 31 AF XY: 0.0187 AC XY: 1370 AN XY: 73430

Gnomad4 AFR AF: 0.0611

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.0127

Gnomad4 SAS AF: 0.00419

Gnomad4 FIN AF: 0.000292

Gnomad4 NFE AF: 0.00124

Gnomad4 OTH AF: 0.0148

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;