16-67195890-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAG

Variant names:

• chr16-67195890-ACAGCAGCAGCAG-A
• rs3830472
• NM_001950.4:c.947_958delGCAGCAGCAGCA

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001950.4(E2F4):​c.947_958delGCAGCAGCAGCA​(p.Ser316_Ser319del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000708 in 1,608,040 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00071 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00071 (1 hom.)
• Consequence: E2F4 NM_001950.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77
• Publications: 11 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001950.4
• BS2: High AC in GnomAd4 at 107 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001950.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F4	NM_001950.4	MANE Select	c.947_958delGCAGCAGCAGCA	p.Ser316_Ser319del	disruptive_inframe_deletion	Exon 7 of 10	NP_001941.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F4	ENST00000379378.8	TSL:1 MANE Select	c.947_958delGCAGCAGCAGCA	p.Ser316_Ser319del	disruptive_inframe_deletion	Exon 7 of 10	ENSP00000368686.3	Q16254
	E2F4	ENST00000914909.1		c.947_958delGCAGCAGCAGCA	p.Ser316_Ser319del	disruptive_inframe_deletion	Exon 7 of 10	ENSP00000584968.1
	E2F4	ENST00000957228.1		c.962_973delGCAGCAGCAGCA	p.Ser321_Ser324del	disruptive_inframe_deletion	Exon 7 of 10	ENSP00000627287.1

Frequencies

GnomAD3 genomes AF: 0.000698 AC: 105 AN: 150350 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000861

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000972

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000681

Gnomad OTH AF: 0.00145

GnomAD4 exome AF: 0.000708 AC: 1032 AN: 1457594 Hom.: 1 AF XY: 0.000743 AC XY: 539 AN XY: 725026

African (AFR) AF: 0.00140 AC: 46 AN: 32860

American (AMR) AF: 0.000337 AC: 15 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.00222 AC: 58 AN: 26076

East Asian (EAS) AF: 0.00106 AC: 42 AN: 39534

South Asian (SAS) AF: 0.00107 AC: 92 AN: 85726

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53052

Middle Eastern (MID) AF: 0.00227 AC: 13 AN: 5730

European-Non Finnish (NFE) AF: 0.000624 AC: 693 AN: 1109936

Other (OTH) AF: 0.00120 AC: 72 AN: 60106

GnomAD4 genome AF: 0.000711 AC: 107 AN: 150446 Hom.: 0 Cov.: 31 AF XY: 0.000708 AC XY: 52 AN XY: 73442

African (AFR) AF: 0.000539 AC: 22 AN: 40830

American (AMR) AF: 0.000860 AC: 13 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3464

East Asian (EAS) AF: 0.000974 AC: 5 AN: 5132

South Asian (SAS) AF: 0.00105 AC: 5 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000681 AC: 46 AN: 67572

Other (OTH) AF: 0.00143 AC: 3 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8
Mutation Taster		=165/35	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3830472; hg19: chr16-67229793;