19-29822696-C-G

Variant names:

• chr19-29822696-C-G
• rs3218070
• NM_001238.4:c.1110+93C>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.1110+93C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,323,612 control chromosomes in the GnomAD database, including 90,976 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 (7486 hom., cov: 31)
  • Exomes 𝑓: 0.37 (83490 hom.)
• Consequence: CCNE1 NM_001238.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• Publications: 4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNE1	NM_001238.4	MANE Select	c.1110+93C>G		intron	N/A	NP_001229.1	P24864-1
	CCNE1	NM_001440305.1		c.1101+93C>G		intron	N/A	NP_001427234.1
	CCNE1	NM_001322262.2		c.1065+93C>G		intron	N/A	NP_001309191.1	P24864-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNE1	ENST00000262643.8	TSL:1 MANE Select	c.1110+93C>G		intron	N/A	ENSP00000262643.3	P24864-1
	CCNE1	ENST00000444983.6	TSL:1	c.1065+93C>G		intron	N/A	ENSP00000410179.2	P24864-3
	CCNE1	ENST00000357943.9	TSL:1	c.930+93C>G		intron	N/A	ENSP00000350625.6	C9J2U0

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42911 AN: 151918 Hom.: 7481 Cov.: 31

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.366 AC: 429383 AN: 1171576 Hom.: 83490 AF XY: 0.365 AC XY: 212151 AN XY: 581986

African (AFR) AF: 0.0746 AC: 2004 AN: 26852

American (AMR) AF: 0.250 AC: 7559 AN: 30290

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 7171 AN: 19050

East Asian (EAS) AF: 0.0995 AC: 3770 AN: 37892

South Asian (SAS) AF: 0.263 AC: 17613 AN: 66872

European-Finnish (FIN) AF: 0.420 AC: 19679 AN: 46888

Middle Eastern (MID) AF: 0.315 AC: 1060 AN: 3366

European-Non Finnish (NFE) AF: 0.397 AC: 353264 AN: 890670

Other (OTH) AF: 0.347 AC: 17263 AN: 49696

GnomAD4 genome AF: 0.282 AC: 42918 AN: 152036 Hom.: 7486 Cov.: 31 AF XY: 0.278 AC XY: 20666 AN XY: 74278

African (AFR) AF: 0.0879 AC: 3651 AN: 41516

American (AMR) AF: 0.256 AC: 3911 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1296 AN: 3470

East Asian (EAS) AF: 0.101 AC: 521 AN: 5184

South Asian (SAS) AF: 0.247 AC: 1187 AN: 4812

European-Finnish (FIN) AF: 0.429 AC: 4508 AN: 10514

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26833 AN: 67964

Other (OTH) AF: 0.293 AC: 618 AN: 2110

Alfa AF: 0.340 Hom.: 1234

Bravo AF: 0.262

Asia WGS AF: 0.142 AC: 495 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	1.7
DANN	Benign	0.66
PhyloP100		-0.12
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: rs3218070; hg19: chr19-30313603; COSMIC: COSV52905717; COSMIC: COSV52905717;