rs1028853905

Variant names:

• chr16-2229586-C-G
• NM_004424.5:c.326C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-2229586-C-G
• chr16-2229586-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004424.5(E4F1):​c.326C>G​(p.Pro109Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P109L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: E4F1 NM_004424.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.836

Genes affected

E4F1 (HGNC:3121): (E4F transcription factor 1) The zinc finger protein encoded by this gene is one of several cellular transcription factors whose DNA-binding activities are regulated through the action of adenovirus E1A. A 50-kDa amino-terminal product is generated from the full-length protein through proteolytic cleavage. The protein is differentially regulated by E1A-induced phosphorylation. The full-length gene product represses transcription from the E4 promoter in the absence of E1A, while the 50-kDa form acts as a transcriptional activator in its presence. Alternative splicing results in multiple transcripts encoding different proteins. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.100503296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E4F1	NM_004424.5	c.326C>G	p.Pro109Arg	missense_variant	Exon 3 of 14	ENST00000301727.9	NP_004415.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E4F1	ENST00000301727.9	c.326C>G	p.Pro109Arg	missense_variant	Exon 3 of 14	1	NM_004424.5	ENSP00000301727.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459362 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726082

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.59
DEOGEN2	Benign	0.073	T;.;.;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;.;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.42	N;N;N;N
REVEL	Benign	0.043
Sift	Uncertain	0.0080	D;T;D;T
Sift4G	Benign	0.45	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.24
MutPred		0.32		Loss of glycosylation at P109 (P = 0.0261);Loss of glycosylation at P109 (P = 0.0261);Loss of glycosylation at P109 (P = 0.0261);.;
MVP		0.50
MPC		0.41
ClinPred		0.23	T
GERP RS		4.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.079
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-2279587;