rs3218036

Variant names:

• chr19-29814777-G-A
• rs3218036
• NM_001238.4:c.180+1740G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001238.4(CCNE1):​c.180+1740G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,034 control chromosomes in the GnomAD database, including 5,121 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 0.23 (5121 hom., cov: 32)
• Consequence: CCNE1 NM_001238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.877
• Publications: 24 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNE1	NM_001238.4	c.180+1740G>A		intron_variant	Intron 4 of 11	ENST00000262643.8	NP_001229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNE1	ENST00000262643.8	c.180+1740G>A		intron_variant	Intron 4 of 11	1	NM_001238.4	ENSP00000262643.3
CCNE1	ENST00000444983.6	c.135+1740G>A		intron_variant	Intron 2 of 9	1		ENSP00000410179.2
CCNE1	ENST00000357943.9	c.135+1740G>A		intron_variant	Intron 2 of 8	1		ENSP00000350625.6
CCNE1	ENST00000575243.5	c.171+1740G>A		intron_variant	Intron 4 of 7	5		ENSP00000459024.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35533 AN: 151916 Hom.: 5119 Cov.: 32

Gnomad AFR AF: 0.0741

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.234 AC: 35531 AN: 152034 Hom.: 5121 Cov.: 32 AF XY: 0.232 AC XY: 17227 AN XY: 74324

African (AFR) AF: 0.0740 AC: 3071 AN: 41498

American (AMR) AF: 0.191 AC: 2917 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1192 AN: 3472

East Asian (EAS) AF: 0.0993 AC: 514 AN: 5174

South Asian (SAS) AF: 0.207 AC: 995 AN: 4814

European-Finnish (FIN) AF: 0.372 AC: 3929 AN: 10550

Middle Eastern (MID) AF: 0.238 AC: 69 AN: 290

European-Non Finnish (NFE) AF: 0.325 AC: 22079 AN: 67954

Other (OTH) AF: 0.240 AC: 503 AN: 2100

Alfa AF: 0.297 Hom.: 3595

Bravo AF: 0.213

Asia WGS AF: 0.122 AC: 427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.68
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

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: rs3218036; hg19: chr19-30305684;