Genetic Variant NM_001760.5:c.415-143C>T (chr6-41937537-G-A) – 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.415-143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 920,002 control chromosomes in the GnomAD database, including 25,658 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 ( 3369 hom., cov: 32)

Exomes 𝑓: 0.23 ( 22289 hom. )

Consequence

CCND3
NM_001760.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.585

Publications

45 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND3	NM_001760.5 link	c.415-143C>T		intron_variant	Intron 2 of 4	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.415-143C>T		intron_variant	Intron 2 of 4	1	NM_001760.5	ENSP00000362082.5		P30281-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29823

AN:

152026

Hom.:

3366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0923

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.179

GnomAD4 exome

AF:

0.232

AC:

177983

AN:

767858

Hom.:

22289

AF XY:

0.230

AC XY:

90047

AN XY:

391006

show subpopulations

African (AFR)

AF:

0.0821

AC:

1547

AN:

18852

American (AMR)

AF:

0.128

AC:

2927

AN:

22812

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

4188

AN:

16272

East Asian (EAS)

AF:

0.220

AC:

7236

AN:

32858

South Asian (SAS)

AF:

0.154

AC:

8396

AN:

54688

European-Finnish (FIN)

AF:

0.237

AC:

7750

AN:

32718

Middle Eastern (MID)

AF:

0.160

AC:

418

AN:

2614

European-Non Finnish (NFE)

AF:

0.249

AC:

137192

AN:

550470

Other (OTH)

AF:

0.228

AC:

8329

AN:

36574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7065

14130

21194

28259

35324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.196

AC:

29828

AN:

152144

Hom.:

3369

Cov.:

AF XY:

0.195

AC XY:

14481

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0920

AC:

3821

AN:

41514

American (AMR)

AF:

0.159

AC:

2432

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

901

AN:

3470

East Asian (EAS)

AF:

0.269

AC:

1393

AN:

5174

South Asian (SAS)

AF:

0.161

AC:

778

AN:

4824

European-Finnish (FIN)

AF:

0.236

AC:

2494

AN:

10588

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17337

AN:

67984

Other (OTH)

AF:

0.180

AC:

381

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1236

2472

3709

4945

6181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.233

Hom.:

14985

Bravo

AF:

0.186

Asia WGS

AF:

0.173

AC:

599

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.2

(source)

DANN

Benign

0.62

PhyloP100

-0.58

Mutation Taster

=100/0

polymorphism (auto)

(source)

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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NM_001760.5:c.415-143C>T

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