dbSNP rs3218074: CCNE1:c.*492A>G (chr19-29824269-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001238.4(CCNE1):c.*492A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000417 in 234,934 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00058 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

CCNE1
NM_001238.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.38

Publications

4 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BS2

High AC in GnomAd4 at 89 AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCNE1	NM_001238.4	MANE Select	c.*492A>G	3_prime_UTR	Exon 12 of 12	NP_001229.1	P24864-1
CCNE1	NM_001440305.1		c.*492A>G	3_prime_UTR	Exon 12 of 12	NP_001427234.1
CCNE1	NM_001322262.2		c.*492A>G	3_prime_UTR	Exon 11 of 11	NP_001309191.1	P24864-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CCNE1	ENST00000262643.8	TSL:1 MANE Select	c.*492A>G	3_prime_UTR	Exon 12 of 12	ENSP00000262643.3	P24864-1
CCNE1	ENST00000357943.9	TSL:1	c.*492A>G	3_prime_UTR	Exon 9 of 9	ENSP00000350625.6	C9J2U0
CCNE1	ENST00000937503.1		c.*492A>G	3_prime_UTR	Exon 13 of 13	ENSP00000607562.1

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000109

AC:

AN:

82652

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

38274

show subpopulations

African (AFR)

AF:

0.00153

AC:

AN:

3920

American (AMR)

AF:

0.00

AC:

AN:

2468

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5066

East Asian (EAS)

AF:

0.00

AC:

AN:

11320

South Asian (SAS)

AF:

0.00

AC:

AN:

710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

502

European-Non Finnish (NFE)

AF:

0.0000587

AC:

AN:

51080

Other (OTH)

AF:

0.00

AC:

AN:

6810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000584

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41552

American (AMR)

AF:

0.000327

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000544

Hom.:

Bravo

AF:

0.000608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

6.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over