16-67195890-ACAGCAGCAGCAGCAGCAGCAGCAGCAGCAG-ACAGCAGCAGCAGCAGCAGCAG

Variant names:

• chr16-67195890-ACAGCAGCAG-A
• rs3830472
• NM_001950.4:c.950_958delGCAGCAGCA

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_001950.4(E2F4):​c.950_958delGCAGCAGCA​(p.Ser317_Ser319del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00292 in 1,608,046 control chromosomes in the GnomAD database, including 27 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.011 (21 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (6 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: Benign. The variant received -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001950.4
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0106 (1593/150436) while in subpopulation AFR AF = 0.0332 (1357/40822). AF 95% confidence interval is 0.0318. There are 21 homozygotes in GnomAd4. There are 761 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1593 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.950_958delGCAGCAGCA	p.Ser317_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.950_958delGCAGCAGCA	p.Ser317_Ser319del	disruptive_inframe_deletion	Exon 7 of 10	ENSP00000368686.3	Q16254
	E2F4	ENST00000914909.1		c.950_958delGCAGCAGCA	p.Ser317_Ser319del	disruptive_inframe_deletion	Exon 7 of 10	ENSP00000584968.1
	E2F4	ENST00000957228.1		c.965_973delGCAGCAGCA	p.Ser322_Ser324del	disruptive_inframe_deletion	Exon 7 of 10	ENSP00000627287.1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1588 AN: 150340 Hom.: 21 Cov.: 31

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00389

Gnomad SAS AF: 0.00293

Gnomad FIN AF: 0.000390

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00145

Gnomad OTH AF: 0.00822

GnomAD4 exome AF: 0.00213 AC: 3099 AN: 1457610 Hom.: 6 AF XY: 0.00210 AC XY: 1522 AN XY: 725030

African (AFR) AF: 0.0325 AC: 1070 AN: 32890

American (AMR) AF: 0.00271 AC: 121 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26076

East Asian (EAS) AF: 0.00427 AC: 169 AN: 39534

South Asian (SAS) AF: 0.00299 AC: 256 AN: 85718

European-Finnish (FIN) AF: 0.000603 AC: 32 AN: 53050

Middle Eastern (MID) AF: 0.00471 AC: 27 AN: 5730

European-Non Finnish (NFE) AF: 0.00111 AC: 1229 AN: 1109932

Other (OTH) AF: 0.00318 AC: 191 AN: 60106

GnomAD4 genome AF: 0.0106 AC: 1593 AN: 150436 Hom.: 21 Cov.: 31 AF XY: 0.0104 AC XY: 761 AN XY: 73436

African (AFR) AF: 0.0332 AC: 1357 AN: 40822

American (AMR) AF: 0.00529 AC: 80 AN: 15118

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

East Asian (EAS) AF: 0.00390 AC: 20 AN: 5132

South Asian (SAS) AF: 0.00314 AC: 15 AN: 4774

European-Finnish (FIN) AF: 0.000390 AC: 4 AN: 10260

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00145 AC: 98 AN: 67572

Other (OTH) AF: 0.00813 AC: 17 AN: 2090

Alfa AF: 0.00130 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8
Mutation Taster		=172/28	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;