rs3218042

Positions:

• chr19-29816431-T-A

Variant summary

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

The NM_001238.4(CCNE1):​c.181-706T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 152,288 control chromosomes in the GnomAD database, including 108 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 (108 hom., cov: 32)
• Consequence: CCNE1 NM_001238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNE1	NM_001238.4	c.181-706T>A		intron_variant		ENST00000262643.8	NP_001229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNE1	ENST00000262643.8	c.181-706T>A		intron_variant		1	NM_001238.4	ENSP00000262643	P1
CCNE1	ENST00000357943.9	c.136-706T>A		intron_variant		1		ENSP00000350625
CCNE1	ENST00000444983.6	c.136-706T>A		intron_variant		1		ENSP00000410179
CCNE1	ENST00000575243.5	c.172-706T>A		intron_variant		5		ENSP00000459024

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1990 AN: 152168 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.00318

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0709

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00909

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

GnomAD4 genome AF: 0.0131 AC: 1994 AN: 152288 Hom.: 108 Cov.: 32 AF XY: 0.0149 AC XY: 1109 AN XY: 74460

Gnomad4 AFR AF: 0.00317

Gnomad4 AMR AF: 0.0712

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.00169

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00693 Hom.: 7

Bravo AF: 0.0210

Asia WGS AF: 0.0460 AC: 160 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.55
DANN	Benign	0.40

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: rs3218042; hg19: chr19-30307338;