rs3218073

Variant names:

• chr19-29824109-C-T
• rs3218073
• NM_001238.4:c.*332C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001238.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNE1	NM_001238.4	MANE Select	c.*332C>T		3_prime_UTR	Exon 12 of 12	NP_001229.1
	CCNE1	NM_001440305.1		c.*332C>T		3_prime_UTR	Exon 12 of 12	NP_001427234.1
	CCNE1	NM_001322262.2		c.*332C>T		3_prime_UTR	Exon 11 of 11	NP_001309191.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNE1	ENST00000262643.8	TSL:1 MANE Select	c.*332C>T		3_prime_UTR	Exon 12 of 12	ENSP00000262643.3
	CCNE1	ENST00000444983.6	TSL:1	c.*332C>T		3_prime_UTR	Exon 10 of 10	ENSP00000410179.2
	CCNE1	ENST00000357943.9	TSL:1	c.*332C>T		3_prime_UTR	Exon 9 of 9	ENSP00000350625.6

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

African (AFR) AF: 0.00324 AC: 18 AN: 5550

American (AMR) AF: 0.0875 AC: 441 AN: 5038

Ashkenazi Jewish (ASJ) AF: 0.000929 AC: 6 AN: 6456

East Asian (EAS) AF: 0.143 AC: 2047 AN: 14356

South Asian (SAS) AF: 0.00162 AC: 6 AN: 3698

European-Finnish (FIN) AF: 0.00207 AC: 11 AN: 5320

Middle Eastern (MID) AF: 0.00137 AC: 1 AN: 730

European-Non Finnish (NFE) AF: 0.000498 AC: 43 AN: 86286

Other (OTH) AF: 0.0114 AC: 112 AN: 9846

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

African (AFR) AF: 0.00310 AC: 129 AN: 41560

American (AMR) AF: 0.0713 AC: 1089 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.137 AC: 710 AN: 5164

South Asian (SAS) AF: 0.00435 AC: 21 AN: 4828

European-Finnish (FIN) AF: 0.00170 AC: 18 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68022

Other (OTH) AF: 0.00949 AC: 20 AN: 2108

Alfa AF: 0.00519 Hom.: 9

Bravo AF: 0.0211

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.51
PhyloP100		1.8
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: rs3218073; hg19: chr19-30315016;