19-29813576-T-C

Variant names:

• chr19-29813576-T-C
• rs997669
• NM_001238.4:c.180+539T>C

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+539T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,038 control chromosomes in the GnomAD database, including 7,762 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 0.29 (7762 hom., cov: 32)
• Consequence: CCNE1 NM_001238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 22 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNE1	NM_001238.4	c.180+539T>C		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+539T>C		intron_variant	Intron 4 of 11	1	NM_001238.4	ENSP00000262643.3

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44804 AN: 151920 Hom.: 7756 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.295 AC: 44822 AN: 152038 Hom.: 7762 Cov.: 32 AF XY: 0.290 AC XY: 21548 AN XY: 74304

African (AFR) AF: 0.127 AC: 5289 AN: 41486

American (AMR) AF: 0.261 AC: 3986 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1333 AN: 3468

East Asian (EAS) AF: 0.101 AC: 523 AN: 5176

South Asian (SAS) AF: 0.247 AC: 1188 AN: 4806

European-Finnish (FIN) AF: 0.430 AC: 4527 AN: 10540

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26950 AN: 67976

Other (OTH) AF: 0.300 AC: 632 AN: 2110

Alfa AF: 0.353 Hom.: 25673

Bravo AF: 0.276

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.5
DANN	Benign	0.55
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs997669; hg19: chr19-30304483;