16-67198781-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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 -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

African (AFR) AF: 0.214 AC: 317 AN: 1482

American (AMR) AF: 0.0439 AC: 166 AN: 3780

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 38 AN: 1806

East Asian (EAS) AF: 0.00762 AC: 29 AN: 3808

South Asian (SAS) AF: 0.0739 AC: 408 AN: 5520

European-Finnish (FIN) AF: 0.0798 AC: 205 AN: 2570

Middle Eastern (MID) AF: 0.0227 AC: 6 AN: 264

European-Non Finnish (NFE) AF: 0.0524 AC: 2044 AN: 39034

Other (OTH) AF: 0.0575 AC: 202 AN: 3510

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

African (AFR) AF: 0.268 AC: 11109 AN: 41492

American (AMR) AF: 0.0543 AC: 831 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 89 AN: 3468

East Asian (EAS) AF: 0.00869 AC: 45 AN: 5176

South Asian (SAS) AF: 0.0920 AC: 444 AN: 4828

European-Finnish (FIN) AF: 0.121 AC: 1285 AN: 10596

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0618 AC: 4204 AN: 68008

Other (OTH) AF: 0.0879 AC: 186 AN: 2116

Alfa AF: 0.0830 Hom.: 2340

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
PhyloP100		3.4
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11700; hg19: chr16-67232684;