8-85189216-T-A

Variant names:

• chr8-85189216-T-A
• rs4150880
• NM_001951.4:c.234+11562T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001951.4(E2F5):​c.234+11562T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,172 control chromosomes in the GnomAD database, including 51,116 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 0.81 (51116 hom., cov: 31)
• Consequence: E2F5 NM_001951.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 3 publications found

Genes affected

E2F5 (HGNC:3119): (E2F transcription factor 5) 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 evolutionarily conserved domains that are present 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 is differentially phosphorylated and is expressed in a wide variety of human tissues. It has higher identity to E2F4 than to other family members. Both this protein and E2F4 interact with tumor suppressor proteins p130 and p107, but not with pRB. Alternative splicing results in multiple variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F5	NM_001951.4	c.234+11562T>A		intron_variant	Intron 1 of 7	ENST00000416274.7	NP_001942.2
E2F5	NM_001083588.2	c.234+11562T>A		intron_variant	Intron 1 of 7		NP_001077057.1
E2F5	NM_001083589.2	c.-250+1420T>A		intron_variant	Intron 1 of 7		NP_001077058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F5	ENST00000416274.7	c.234+11562T>A		intron_variant	Intron 1 of 7	1	NM_001951.4	ENSP00000398124.2

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123592 AN: 152052 Hom.: 51057 Cov.: 31

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.813 AC: 123709 AN: 152172 Hom.: 51116 Cov.: 31 AF XY: 0.811 AC XY: 60341 AN XY: 74372

African (AFR) AF: 0.948 AC: 39396 AN: 41540

American (AMR) AF: 0.705 AC: 10775 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2628 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3141 AN: 5176

South Asian (SAS) AF: 0.729 AC: 3519 AN: 4826

European-Finnish (FIN) AF: 0.866 AC: 9156 AN: 10578

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.773 AC: 52564 AN: 67990

Other (OTH) AF: 0.807 AC: 1703 AN: 2110

Alfa AF: 0.752 Hom.: 2325

Bravo AF: 0.806

Asia WGS AF: 0.708 AC: 2460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.4
DANN	Benign	0.59
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4150880; hg19: chr8-86101451;