rs3218108

Positions:

• chr6-41934917-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

Genes affected

(HGNC:):

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CCND3	NM_001760.5	c.*1023G>A		downstream_gene_variant		ENST00000372991.9	NP_001751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND3	ENST00000372991.9	c.*1023G>A		downstream_gene_variant		1	NM_001760.5	ENSP00000362082.5

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29791 AN: 152098 Hom.: 3328 Cov.: 33

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.: 0 AF XY: 0.237 AC XY: 7567 AN XY: 31970

Gnomad4 AFR exome AF: 0.0762

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.196 AC: 29809 AN: 152216 Hom.: 3330 Cov.: 33 AF XY: 0.195 AC XY: 14526 AN XY: 74416

Gnomad4 AFR AF: 0.0875

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.193

Alfa AF: 0.238 Hom.: 4939

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
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3218108; hg19: chr6-41902655;