rs2403083

Positions:

• chr8-85195914-C-A
• chr8-85195914-C-G
• chr8-85195914-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001951.4(E2F5):​c.235-6233C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,082 control chromosomes in the GnomAD database, including 36,268 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 0.68 (36268 hom., cov: 33)
• Consequence: E2F5 NM_001951.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
E2F5	NM_001951.4	c.235-6233C>A		intron_variant		ENST00000416274.7	NP_001942.2
E2F5	NM_001083588.2	c.235-6233C>A		intron_variant			NP_001077057.1
E2F5	NM_001083589.2	c.-249-6233C>A		intron_variant			NP_001077058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
E2F5	ENST00000416274.7	c.235-6233C>A		intron_variant		1	NM_001951.4	ENSP00000398124.2

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103683 AN: 151964 Hom.: 36241 Cov.: 33

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.682 AC: 103750 AN: 152082 Hom.: 36268 Cov.: 33 AF XY: 0.683 AC XY: 50761 AN XY: 74358

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.853

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.684

Alfa AF: 0.671 Hom.: 2294

Bravo AF: 0.661

Asia WGS AF: 0.488 AC: 1696 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.22

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

LitVar

Other links and lift over

dbSNP: rs2403083; hg19: chr8-86108149;