11-69641449-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_053056.3(CCND1):ā€‹c.136A>Gā€‹(p.Lys46Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CCND1
NM_053056.3 missense

Scores

1
4
14

Clinical Significance

- - O:1

Conservation

PhyloP100: 6.39
Variant links:
Genes affected
CCND1 (HGNC:1582): (cyclin D1) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout 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 CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of human cancers. [provided by RefSeq, Dec 2019]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39724994).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCND1NM_053056.3 linkuse as main transcriptc.136A>G p.Lys46Glu missense_variant 1/5 ENST00000227507.3 NP_444284.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCND1ENST00000227507.3 linkuse as main transcriptc.136A>G p.Lys46Glu missense_variant 1/51 NM_053056.3 ENSP00000227507 P1
CCND1ENST00000536559.1 linkuse as main transcriptc.136A>G p.Lys46Glu missense_variant 1/23 ENSP00000438482
CCND1ENST00000535993.1 linkuse as main transcriptn.219A>G non_coding_transcript_exon_variant 1/22
CCND1ENST00000539241.1 linkuse as main transcriptn.285A>G non_coding_transcript_exon_variant 1/32

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1461162
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726894
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: -
Submissions summary: Other:1
Revision: -
LINK: link

Submissions by phenotype

Neoplasm Other:1
-, criteria provided, single submitterclinical testingCenter for Genomic Medicine, Rigshospitalet, Copenhagen University HospitalJul 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Benign
-0.047
T
BayesDel_noAF
Benign
-0.31
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T;T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.053
FATHMM_MKL
Benign
0.56
D
LIST_S2
Uncertain
0.87
D;T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.40
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.70
N;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-1.3
N;N
REVEL
Uncertain
0.30
Sift
Benign
0.41
T;T
Sift4G
Benign
0.35
T;T
Polyphen
0.012
B;.
Vest4
0.55
MutPred
0.42
Loss of methylation at K46 (P = 6e-04);Loss of methylation at K46 (P = 6e-04);
MVP
0.67
MPC
2.0
ClinPred
0.90
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.74
gMVP
0.44

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs747665638; hg19: chr11-69456217; COSMIC: COSV57121092; COSMIC: COSV57121092; API