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GeneBe

6-41936586-C-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001760.5(CCND3):c.684G>C(p.Leu228=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,614,206 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0030 ( 12 hom. )

Consequence

CCND3
NM_001760.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.43
Variant links:
Genes affected
CCND3 (HGNC:1585): (cyclin D3) 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 CDK4 or CDK6, whose activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-41936586-C-G is Benign according to our data. Variant chr6-41936586-C-G is described in ClinVar as [Benign]. Clinvar id is 711316.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.43 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 278 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCND3NM_001760.5 linkuse as main transcriptc.684G>C p.Leu228= synonymous_variant 4/5 ENST00000372991.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCND3ENST00000372991.9 linkuse as main transcriptc.684G>C p.Leu228= synonymous_variant 4/51 NM_001760.5 P1P30281-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00183
AC:
278
AN:
152226
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00403
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00354
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.00171
AC:
431
AN:
251338
Hom.:
2
AF XY:
0.00179
AC XY:
243
AN XY:
135848
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.000752
Gnomad ASJ exome
AF:
0.00655
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.00279
Gnomad OTH exome
AF:
0.00245
GnomAD4 exome
AF:
0.00301
AC:
4399
AN:
1461862
Hom.:
12
Cov.:
31
AF XY:
0.00296
AC XY:
2154
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.000418
Gnomad4 AMR exome
AF:
0.000850
Gnomad4 ASJ exome
AF:
0.00696
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000262
Gnomad4 NFE exome
AF:
0.00346
Gnomad4 OTH exome
AF:
0.00498
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00182
AC:
277
AN:
152344
Hom.:
0
Cov.:
32
AF XY:
0.00169
AC XY:
126
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.000433
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00403
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.00353
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.00302
Hom.:
0
Bravo
AF:
0.00196
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00398
EpiControl
AF:
0.00207

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
11
Dann
Benign
0.87
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs11552780; hg19: chr6-41904324; COSMIC: COSV57827841; COSMIC: COSV57827841; API