rs11700

Variant names:

• chr16-67198781-A-G
• rs11700
• NM_001950.4:c.*658A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001950.4(E2F4):​c.*658A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 213,958 control chromosomes in the GnomAD database, including 1,948 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1773 hom., cov: 33)
  • Exomes 𝑓: 0.055 (175 hom.)
• Consequence: E2F4 NM_001950.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.37

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F4	NM_001950.4	c.*658A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000379378.8	NP_001941.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F4	ENST00000379378.8	c.*658A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_001950.4	ENSP00000368686.3
E2F4	ENST00000567007.5	n.2479A>G		non_coding_transcript_exon_variant	Exon 8 of 8	2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18276 AN: 152066 Hom.: 1767 Cov.: 33

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.0917

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0618

Gnomad OTH AF: 0.0879

GnomAD4 exome AF: 0.0553 AC: 3415 AN: 61774 Hom.: 175 Cov.: 0 AF XY: 0.0547 AC XY: 1736 AN XY: 31760

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.0439

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.00762

Gnomad4 SAS exome AF: 0.0739

Gnomad4 FIN exome AF: 0.0798

Gnomad4 NFE exome AF: 0.0524

Gnomad4 OTH exome AF: 0.0575

GnomAD4 genome AF: 0.120 AC: 18307 AN: 152184 Hom.: 1773 Cov.: 33 AF XY: 0.121 AC XY: 8997 AN XY: 74400

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.0543

Gnomad4 ASJ AF: 0.0257

Gnomad4 EAS AF: 0.00869

Gnomad4 SAS AF: 0.0920

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.0618

Gnomad4 OTH AF: 0.0879

Alfa AF: 0.0697 Hom.: 811

Bravo AF: 0.120

Asia WGS AF: 0.0840 AC: 293 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11700; hg19: chr16-67232684;