rs3218086

Variant names:

• chr6-41942326-C-T
• rs3218086
• ENST00000372988.8:c.-45-1741G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136017.3(CCND3):​c.-45-1741G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,126 control chromosomes in the GnomAD database, including 2,977 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 0.18 (2977 hom., cov: 31)
• Consequence: CCND3 NM_001136017.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514
• Publications: 10 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136017.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND3	NM_001136017.3		c.-45-1741G>A		intron	N/A	NP_001129489.1
	CCND3	NM_001424053.1		c.-45-1741G>A		intron	N/A	NP_001410982.1
	CCND3	NM_001424055.1		c.-45-1741G>A		intron	N/A	NP_001410984.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND3	ENST00000372988.8	TSL:1	c.-45-1741G>A		intron	N/A	ENSP00000362079.4
	CCND3	ENST00000511642.5	TSL:2	c.-45-1741G>A		intron	N/A	ENSP00000426212.1
	CCND3	ENST00000510503.5	TSL:3	c.-45-1741G>A		intron	N/A	ENSP00000425986.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27602 AN: 152008 Hom.: 2965 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.182 AC: 27629 AN: 152126 Hom.: 2977 Cov.: 31 AF XY: 0.190 AC XY: 14106 AN XY: 74350

African (AFR) AF: 0.108 AC: 4491 AN: 41528

American (AMR) AF: 0.276 AC: 4216 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3470

East Asian (EAS) AF: 0.387 AC: 2000 AN: 5168

South Asian (SAS) AF: 0.377 AC: 1817 AN: 4822

European-Finnish (FIN) AF: 0.203 AC: 2145 AN: 10572

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12041 AN: 67990

Other (OTH) AF: 0.175 AC: 369 AN: 2110

Alfa AF: 0.174 Hom.: 2726

Bravo AF: 0.184

Asia WGS AF: 0.347 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.8
DANN	Benign	0.82
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3218086; hg19: chr6-41910064;