16-67195890-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG

Variant names:

• chr16-67195890-A-ACAGCAGCAGCAG
• rs3830472
• NM_001950.4:c.947_958dupGCAGCAGCAGCA

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BA1

The NM_001950.4(E2F4):​c.947_958dupGCAGCAGCAGCA​(p.Ser316_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 0.0033 in 1,607,958 control chromosomes in the GnomAD database, including 78 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.016 (67 hom., cov: 31)
  • Exomes 𝑓: 0.0020 (11 hom.)
• Consequence: E2F4 NM_001950.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• 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: Benign. The variant received -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001950.4
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

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_958dupGCAGCAGCAGCA	p.Ser316_Ser319dup	disruptive_inframe_insertion	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_958dupGCAGCAGCAGCA	p.Ser316_Ser319dup	disruptive_inframe_insertion	Exon 7 of 10	ENSP00000368686.3	Q16254
	E2F4	ENST00000914909.1		c.947_958dupGCAGCAGCAGCA	p.Ser316_Ser319dup	disruptive_inframe_insertion	Exon 7 of 10	ENSP00000584968.1
	E2F4	ENST00000957228.1		c.962_973dupGCAGCAGCAGCA	p.Ser321_Ser324dup	disruptive_inframe_insertion	Exon 7 of 10	ENSP00000627287.1

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2348 AN: 150338 Hom.: 67 Cov.: 31

Gnomad AFR AF: 0.0537

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00642

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000972

Gnomad SAS AF: 0.000627

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000488

Gnomad OTH AF: 0.00966

GnomAD4 exome AF: 0.00202 AC: 2949 AN: 1457524 Hom.: 11 Cov.: 30 AF XY: 0.00185 AC XY: 1342 AN XY: 725002

African (AFR) AF: 0.0609 AC: 2000 AN: 32822

American (AMR) AF: 0.00321 AC: 143 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26076

East Asian (EAS) AF: 0.00422 AC: 167 AN: 39532

South Asian (SAS) AF: 0.000280 AC: 24 AN: 85728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53052

Middle Eastern (MID) AF: 0.00628 AC: 36 AN: 5728

European-Non Finnish (NFE) AF: 0.000311 AC: 345 AN: 1109918

Other (OTH) AF: 0.00384 AC: 231 AN: 60102

GnomAD4 genome AF: 0.0157 AC: 2360 AN: 150434 Hom.: 67 Cov.: 31 AF XY: 0.0152 AC XY: 1116 AN XY: 73432

African (AFR) AF: 0.0539 AC: 2199 AN: 40822

American (AMR) AF: 0.00648 AC: 98 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

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

South Asian (SAS) AF: 0.000628 AC: 3 AN: 4774

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

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000488 AC: 33 AN: 67570

Other (OTH) AF: 0.00908 AC: 19 AN: 2092

Alfa AF: 0.00102 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
Mutation Taster		=75/25	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;