rs3218038

Variant names:

• chr19-29814988-G-T
• rs3218038
• NM_001238.4:c.180+1951G>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.180+1951G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,204 control chromosomes in the GnomAD database, including 1,025 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 0.091 (1025 hom., cov: 33)
• Consequence: CCNE1 NM_001238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNE1	NM_001238.4	c.180+1951G>T		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+1951G>T		intron_variant	Intron 4 of 11	1	NM_001238.4	ENSP00000262643.3
CCNE1	ENST00000444983.6	c.135+1951G>T		intron_variant	Intron 2 of 9	1		ENSP00000410179.2
CCNE1	ENST00000357943.9	c.135+1951G>T		intron_variant	Intron 2 of 8	1		ENSP00000350625.6
CCNE1	ENST00000575243.5	c.171+1951G>T		intron_variant	Intron 4 of 7	5		ENSP00000459024.1

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13867 AN: 152086 Hom.: 1018 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.0401

Gnomad FIN AF: 0.0292

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0378

Gnomad OTH AF: 0.0779

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

GnomAD4 genome AF: 0.0914 AC: 13905 AN: 152204 Hom.: 1025 Cov.: 33 AF XY: 0.0924 AC XY: 6872 AN XY: 74400

African (AFR) AF: 0.174 AC: 7217 AN: 41496

American (AMR) AF: 0.124 AC: 1893 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0686 AC: 238 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1256 AN: 5180

South Asian (SAS) AF: 0.0393 AC: 190 AN: 4830

European-Finnish (FIN) AF: 0.0292 AC: 309 AN: 10596

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0378 AC: 2571 AN: 68022

Other (OTH) AF: 0.0766 AC: 162 AN: 2114

Alfa AF: 0.0636 Hom.: 1188

Bravo AF: 0.105

Asia WGS AF: 0.141 AC: 489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.47
PhyloP100		-0.92
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: rs3218038; hg19: chr19-30305895;