dbSNP rs3218108: CCND3:c.*1023G>A (chr6-41934917-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001760.5(CCND3):c.*1023G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 221,392 control chromosomes in the GnomAD database, including 5,349 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 0.20 ( 3330 hom., cov: 33)

Exomes 𝑓: 0.23 ( 2019 hom. )

Consequence

CCND3
NM_001760.5 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.27

Publications

14 publications found

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]

CCND3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND3	NM_001760.5 link	c.*1023G>A		downstream_gene_variant		ENST00000372991.9	NP_001751.1	P30281-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCND3	ENST00000372991.9 link	c.*1023G>A		downstream_gene_variant		1	NM_001760.5	ENSP00000362082.5		P30281-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29791

AN:

152098

Hom.:

3328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0874

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.289

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.240

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.191

GnomAD4 exome

AF:

0.232

AC:

16071

AN:

69176

Hom.:

2019

Cov.:

AF XY:

0.237

AC XY:

7567

AN XY:

31970

show subpopulations

African (AFR)

AF:

0.0762

AC:

246

AN:

3228

American (AMR)

AF:

0.150

AC:

313

AN:

2080

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

1151

AN:

4348

East Asian (EAS)

AF:

0.199

AC:

1999

AN:

10052

South Asian (SAS)

AF:

0.126

AC:

AN:

594

European-Finnish (FIN)

AF:

0.140

AC:

AN:

Middle Eastern (MID)

AF:

0.183

AC:

AN:

432

European-Non Finnish (NFE)

AF:

0.253

AC:

10785

AN:

42612

Other (OTH)

AF:

0.245

AC:

1416

AN:

5780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

600

1201

1801

2402

3002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.196

AC:

29809

AN:

152216

Hom.:

3330

Cov.:

AF XY:

0.195

AC XY:

14526

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0875

AC:

3637

AN:

41562

American (AMR)

AF:

0.166

AC:

2542

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

912

AN:

3468

East Asian (EAS)

AF:

0.289

AC:

1496

AN:

5180

South Asian (SAS)

AF:

0.157

AC:

757

AN:

4832

European-Finnish (FIN)

AF:

0.240

AC:

2534

AN:

10564

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.253

AC:

17220

AN:

67994

Other (OTH)

AF:

0.193

AC:

407

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1256

2511

3767

5022

6278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.226

Hom.:

7064

Bravo

AF:

0.186

Asia WGS

AF:

0.182

AC:

632

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

9.3

(source)

DANN

Benign

0.63

PhyloP100

1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs3218108

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over