rs3218076

Variant names:

• chr19-29824363-T-G
• rs3218076
• NM_001238.4:c.*586T>G

Variant summary

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

The NM_001238.4(CCNE1):​c.*586T>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 196,756 control chromosomes in the GnomAD database, including 12,270 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 0.35 (10234 hom., cov: 30)
  • Exomes 𝑓: 0.26 (2036 hom.)
• Consequence: CCNE1 NM_001238.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNE1	NM_001238.4	c.*586T>G		downstream_gene_variant		ENST00000262643.8	NP_001229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNE1	ENST00000262643.8	c.*586T>G		downstream_gene_variant		1	NM_001238.4	ENSP00000262643.3
CCNE1	ENST00000444983.6	c.*586T>G		downstream_gene_variant		1		ENSP00000410179.2
CCNE1	ENST00000357943.9	c.*586T>G		downstream_gene_variant		1		ENSP00000350625.6
CCNE1	ENST00000574121.1	n.*83T>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53319 AN: 151012 Hom.: 10203 Cov.: 30

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.318

GnomAD4 exome AF: 0.257 AC: 11715 AN: 45624 Hom.: 2036 AF XY: 0.256 AC XY: 5435 AN XY: 21232

African (AFR) AF: 0.392 AC: 658 AN: 1680

American (AMR) AF: 0.316 AC: 353 AN: 1116

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 587 AN: 2936

East Asian (EAS) AF: 0.486 AC: 3416 AN: 7032

South Asian (SAS) AF: 0.408 AC: 147 AN: 360

European-Finnish (FIN) AF: 0.302 AC: 116 AN: 384

Middle Eastern (MID) AF: 0.134 AC: 41 AN: 306

European-Non Finnish (NFE) AF: 0.195 AC: 5461 AN: 28064

Other (OTH) AF: 0.250 AC: 936 AN: 3746

GnomAD4 genome AF: 0.353 AC: 53391 AN: 151132 Hom.: 10234 Cov.: 30 AF XY: 0.358 AC XY: 26446 AN XY: 73802

African (AFR) AF: 0.490 AC: 20108 AN: 41062

American (AMR) AF: 0.398 AC: 6010 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 863 AN: 3464

East Asian (EAS) AF: 0.480 AC: 2465 AN: 5140

South Asian (SAS) AF: 0.453 AC: 2172 AN: 4792

European-Finnish (FIN) AF: 0.276 AC: 2857 AN: 10348

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17795 AN: 67910

Other (OTH) AF: 0.325 AC: 682 AN: 2100

Alfa AF: 0.328 Hom.: 1954

Bravo AF: 0.365

Asia WGS AF: 0.545 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.50
PhyloP100		-0.045

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3218076; hg19: chr19-30315270;