rs3218097

chr6-41937537-G-Achr6-41937537-G-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CCND3	NM_001760.5	c.415-143C>T		intron_variant		ENST00000372991.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCND3	ENST00000372991.9	c.415-143C>T		intron_variant		1	NM_001760.5	P1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29823 AN: 152026 Hom.: 3366 Cov.: 32

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

Gnomad4 AFR exome AF: 0.0821

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.196 AC: 29828 AN: 152144 Hom.: 3369 Cov.: 32 AF XY: 0.195 AC XY: 14481 AN XY: 74378

Gnomad4 AFR AF: 0.0920

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.180

Alfa AF: 0.242 Hom.: 10283

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
Dann	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs3218097; hg19: chr6-41905275;