rs1406

Positions:

• chr19-29824205-C-A
• chr19-29824205-C-T

Variant summary

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

The NM_001238.4(CCNE1):​c.*428C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 249,640 control chromosomes in the GnomAD database, including 9,380 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 0.28 (6188 hom., cov: 32)
  • Exomes 𝑓: 0.25 (3192 hom.)
• Consequence: CCNE1 NM_001238.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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]

CCNE1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNE1	NM_001238.4	c.*428C>A		3_prime_UTR_variant	12/12	ENST00000262643.8	NP_001229.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNE1	ENST00000262643.8	c.*428C>A		3_prime_UTR_variant	12/12	1	NM_001238.4	ENSP00000262643.3
CCNE1	ENST00000444983.6	c.*428C>A		3_prime_UTR_variant	10/10	1		ENSP00000410179.2
CCNE1	ENST00000357943.9	c.*428C>A		3_prime_UTR_variant	9/9	1		ENSP00000350625.6
CCNE1	ENST00000574121.1	n.1220C>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42209 AN: 151890 Hom.: 6172 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.246 AC: 23971 AN: 97632 Hom.: 3192 Cov.: 0 AF XY: 0.243 AC XY: 11214 AN XY: 46084

Gnomad4 AFR exome AF: 0.323

Gnomad4 AMR exome AF: 0.345

Gnomad4 ASJ exome AF: 0.163

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.211

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.278 AC: 42243 AN: 152008 Hom.: 6188 Cov.: 32 AF XY: 0.284 AC XY: 21095 AN XY: 74288

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.255

Alfa AF: 0.231 Hom.: 8718

Bravo AF: 0.282

Asia WGS AF: 0.448 AC: 1557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1406; hg19: chr19-30315112;