19-29822669-C-T

Variant names:

• chr19-29822669-C-T
• rs3218069
• NM_001238.4:c.1110+66C>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.1110+66C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,512,874 control chromosomes in the GnomAD database, including 105,719 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 0.30 (7757 hom., cov: 31)
  • Exomes 𝑓: 0.37 (97962 hom.)
• Consequence: CCNE1 NM_001238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 8 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 (NFE) allele frequency at 95% confidence interval = 0.391 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.1110+66C>T		intron	N/A	NP_001229.1
	CCNE1	NM_001440305.1		c.1101+66C>T		intron	N/A	NP_001427234.1
	CCNE1	NM_001322262.2		c.1065+66C>T		intron	N/A	NP_001309191.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNE1	ENST00000262643.8	TSL:1 MANE Select	c.1110+66C>T		intron	N/A	ENSP00000262643.3
	CCNE1	ENST00000444983.6	TSL:1	c.1065+66C>T		intron	N/A	ENSP00000410179.2
	CCNE1	ENST00000357943.9	TSL:1	c.930+66C>T		intron	N/A	ENSP00000350625.6

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45165 AN: 151808 Hom.: 7752 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.309

GnomAD4 exome AF: 0.371 AC: 504916 AN: 1360948 Hom.: 97962 AF XY: 0.369 AC XY: 248059 AN XY: 672176

African (AFR) AF: 0.128 AC: 3989 AN: 31102

American (AMR) AF: 0.250 AC: 9533 AN: 38088

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 8241 AN: 21908

East Asian (EAS) AF: 0.0991 AC: 3856 AN: 38922

South Asian (SAS) AF: 0.265 AC: 20205 AN: 76146

European-Finnish (FIN) AF: 0.421 AC: 21404 AN: 50850

Middle Eastern (MID) AF: 0.317 AC: 1271 AN: 4014

European-Non Finnish (NFE) AF: 0.399 AC: 416622 AN: 1043698

Other (OTH) AF: 0.352 AC: 19795 AN: 56220

GnomAD4 genome AF: 0.297 AC: 45175 AN: 151926 Hom.: 7757 Cov.: 31 AF XY: 0.293 AC XY: 21761 AN XY: 74226

African (AFR) AF: 0.139 AC: 5779 AN: 41448

American (AMR) AF: 0.262 AC: 3990 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3470

East Asian (EAS) AF: 0.101 AC: 522 AN: 5176

South Asian (SAS) AF: 0.248 AC: 1190 AN: 4808

European-Finnish (FIN) AF: 0.429 AC: 4512 AN: 10510

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26846 AN: 67950

Other (OTH) AF: 0.306 AC: 645 AN: 2110

Alfa AF: 0.374 Hom.: 6017

Bravo AF: 0.279

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.59
PhyloP100		0.0060
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: rs3218069; hg19: chr19-30313576; COSMIC: COSV52904682; COSMIC: COSV52904682;