11-19224727-AT-GA

Variant names:

• chr11-19224727-AT-GA
• NM_024680.4:c.2534_2535delATinsTC
• E2F8 p.Asn845Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_024680.4(E2F8):​c.2534_2535delATinsTC​(p.Asn845Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. N845S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: E2F8 NM_024680.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 0 publications found

Genes affected

E2F8 (HGNC:24727): (E2F transcription factor 8) This gene encodes a member of a family of transcription factors which regulate the expression of genes required for progression through the cell cycle. The encoded protein regulates progression from G1 to S phase by ensuring the nucleus divides at the proper time. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2012]

CSRP3-AS1 (HGNC:54183): (CSRP3 and E2F8 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024680.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F8	NM_024680.4	MANE Select	c.2534_2535delATinsTC	p.Asn845Ile	missense	N/A	NP_078956.2
	E2F8	NM_001256371.2		c.2534_2535delATinsTC	p.Asn845Ile	missense	N/A	NP_001243300.1	A0AVK6
	E2F8	NM_001256372.1		c.2534_2535delATinsTC	p.Asn845Ile	missense	N/A	NP_001243301.1	A0AVK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	E2F8	ENST00000250024.9	TSL:1 MANE Select	c.2534_2535delATinsTC	p.Asn845Ile	missense	N/A	ENSP00000250024.4	A0AVK6
	E2F8	ENST00000928104.1		c.2558_2559delATinsTC	p.Asn853Ile	missense	N/A	ENSP00000598163.1
	E2F8	ENST00000527884.5	TSL:2	c.2534_2535delATinsTC	p.Asn845Ile	missense	N/A	ENSP00000434199.1	A0AVK6

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.34

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-19246274;