19-29824205-C-T

Variant names:

• chr19-29824205-C-T
• rs1406
• NM_001238.4:c.*428C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001238.4(CCNE1):​c.*428C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCNE1 NM_001238.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 23 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNE1	NM_001238.4	c.*428C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000262643.8	NP_001229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNE1	ENST00000262643.8	c.*428C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_001238.4	ENSP00000262643.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 97798 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 46166

African (AFR) AF: 0.00 AC: 0 AN: 4370

American (AMR) AF: 0.00 AC: 0 AN: 3144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5516

East Asian (EAS) AF: 0.00 AC: 0 AN: 12236

South Asian (SAS) AF: 0.00 AC: 0 AN: 1002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61246

Other (OTH) AF: 0.00 AC: 0 AN: 7714

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.4
DANN	Benign	0.45
PhyloP100		0.080
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1406; hg19: chr19-30315112;