NM_024680.4:c.2534A>T

Variant names:

• chr11-19224728-T-A
• NM_024680.4:c.2534A>T

Variant summary

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

The NM_024680.4(E2F8):​c.2534A>T​(p.Asn845Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: E2F8 NM_024680.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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

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=0.07719174).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
E2F8	NM_024680.4	c.2534A>T	p.Asn845Ile	missense_variant	Exon 13 of 13	ENST00000250024.9	NP_078956.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
E2F8	ENST00000250024.9	c.2534A>T	p.Asn845Ile	missense_variant	Exon 13 of 13	1	NM_024680.4	ENSP00000250024.4
E2F8	ENST00000527884.5	c.2534A>T	p.Asn845Ile	missense_variant	Exon 13 of 13	2		ENSP00000434199.1
E2F8	ENST00000620009.4	c.2534A>T	p.Asn845Ile	missense_variant	Exon 13 of 13	5		ENSP00000481103.1
CSRP3-AS1	ENST00000527978.1	n.146-106T>A		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.40	T;T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.69	.;T;.
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M;M
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.6	D;.;D
REVEL	Benign	0.051
Sift	Uncertain	0.0050	D;.;D
Sift4G	Uncertain	0.035	D;D;D
Polyphen		0.41	B;B;B
Vest4		0.26
MutPred		0.21		Loss of disorder (P = 0.0275);Loss of disorder (P = 0.0275);Loss of disorder (P = 0.0275);
MVP		0.093
MPC		0.22
ClinPred		0.48	T
GERP RS		-1.6
Varity_R		0.18
gMVP		0.31

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-19246275;