chr19-29824109-C-T

Position:

• chr19-29824109-C-T

Variant summary

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

The NM_001238.4(CCNE1):​c.*332C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0162 in 289,518 control chromosomes in the GnomAD database, including 295 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 0.013 (117 hom., cov: 33)
  • Exomes 𝑓: 0.020 (178 hom.)
• Consequence: CCNE1 NM_001238.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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]

CCNE1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNE1	NM_001238.4	c.*332C>T		3_prime_UTR_variant	12/12	ENST00000262643.8	NP_001229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNE1	ENST00000262643.8	c.*332C>T		3_prime_UTR_variant	12/12	1	NM_001238.4	ENSP00000262643.3
CCNE1	ENST00000444983.6	c.*332C>T		3_prime_UTR_variant	10/10	1		ENSP00000410179.2
CCNE1	ENST00000357943.9	c.*332C>T		3_prime_UTR_variant	9/9	1		ENSP00000350625.6
CCNE1	ENST00000574121.1	n.1124C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2004 AN: 152120 Hom.: 116 Cov.: 33

Gnomad AFR AF: 0.00311

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.00455

Gnomad FIN AF: 0.00170

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00959

GnomAD4 exome AF: 0.0196 AC: 2685 AN: 137280 Hom.: 178 Cov.: 0 AF XY: 0.0187 AC XY: 1241 AN XY: 66540

Gnomad4 AFR exome AF: 0.00324

Gnomad4 AMR exome AF: 0.0875

Gnomad4 ASJ exome AF: 0.000929

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.00162

Gnomad4 FIN exome AF: 0.00207

Gnomad4 NFE exome AF: 0.000498

Gnomad4 OTH exome AF: 0.0114

GnomAD4 genome AF: 0.0132 AC: 2009 AN: 152238 Hom.: 117 Cov.: 33 AF XY: 0.0150 AC XY: 1118 AN XY: 74434

Gnomad4 AFR AF: 0.00310

Gnomad4 AMR AF: 0.0713

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.00170

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00949

Alfa AF: 0.00552 Hom.: 9

Bravo AF: 0.0211

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.51

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: rs3218073; hg19: chr19-30315016;