rs3218070

Positions:

• chr19-29822696-C-G

Variant summary

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

The NM_001238.4(CCNE1):​c.1110+93C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,323,612 control chromosomes in the GnomAD database, including 90,976 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 0.28 (7486 hom., cov: 31)
  • Exomes 𝑓: 0.37 (83490 hom.)
• Consequence: CCNE1 NM_001238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120

Genes affected

CCNE1 (HGNC:1589): (cyclin E1) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK2, whose activity is required for cell cycle G1/S transition. This protein accumulates at the G1-S phase boundary and is degraded as cells progress through S phase. Overexpression of this gene has been observed in many tumors, which results in chromosome instability, and thus may contribute to tumorigenesis. This protein was found to associate with, and be involved in, the phosphorylation of NPAT protein (nuclear protein mapped to the ATM locus), which participates in cell-cycle regulated histone gene expression and plays a critical role in promoting cell-cycle progression in the absence of pRB. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNE1	NM_001238.4	c.1110+93C>G		intron_variant		ENST00000262643.8	NP_001229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNE1	ENST00000262643.8	c.1110+93C>G		intron_variant		1	NM_001238.4	ENSP00000262643	P1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42911 AN: 151918 Hom.: 7481 Cov.: 31

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.366 AC: 429383 AN: 1171576 Hom.: 83490 AF XY: 0.365 AC XY: 212151 AN XY: 581986

Gnomad4 AFR exome AF: 0.0746

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.376

Gnomad4 EAS exome AF: 0.0995

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.282 AC: 42918 AN: 152036 Hom.: 7486 Cov.: 31 AF XY: 0.278 AC XY: 20666 AN XY: 74278

Gnomad4 AFR AF: 0.0879

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.373

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.293

Alfa AF: 0.340 Hom.: 1234

Bravo AF: 0.262

Asia WGS AF: 0.142 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.66

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: rs3218070; hg19: chr19-30313603; COSMIC: COSV52905717; COSMIC: COSV52905717;