dbSNP rs9349205: CCND3:c.-45-16836C>T (chr6-41957421-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001136017.3(CCND3):c.-45-16836C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,138 control chromosomes in the GnomAD database, including 2,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 2977 hom., cov: 32)

Consequence

CCND3
NM_001136017.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.680

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 6-41957421-G-A is Benign according to our data. Variant chr6-41957421-G-A is described in ClinVar as [Benign]. Clinvar id is 1282713.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
CCND3	NM_001136017.3 link	c.-45-16836C>T	intron_variant	Intron 1 of 4	NP_001129489.1	P30281-2
CCND3	NM_001424053.1 link	c.-45-16836C>T	intron_variant	Intron 1 of 4	NP_001410982.1
CCND3	NM_001424055.1 link	c.-45-16836C>T	intron_variant	Intron 2 of 5	NP_001410984.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
CCND3	ENST00000372988.8 link	c.-45-16836C>T	intron_variant	Intron 1 of 4	1	ENSP00000362079.4	P30281-2
CCND3	ENST00000511642.5 link	c.-45-16836C>T	intron_variant	Intron 1 of 4	2	ENSP00000426212.1	P30281-2
CCND3	ENST00000510503.5 link	c.-45-16836C>T	intron_variant	Intron 1 of 3	3	ENSP00000425986.1	D6RI00

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26886

AN:

152020

Hom.:

2974

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0509

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.177

AC:

26891

AN:

152138

Hom.:

2977

Cov.:

AF XY:

0.177

AC XY:

13142

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0508

Gnomad4 AMR

AF:

0.145

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.270

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.243

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.229

Hom.:

5290

Bravo

AF:

0.166

Asia WGS

AF:

0.171

AC:

594

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 23, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 22929040) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

3.7

DANN

Benign

0.70

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over