rs2479717

Positions:

• chr6-41937436-T-A
• chr6-41937436-T-G

Variant summary

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

The NM_001760.5(CCND3):​c.415-42A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,610,590 control chromosomes in the GnomAD database, including 467,463 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 0.81 (50320 hom., cov: 31)
  • Exomes 𝑓: 0.75 (417143 hom.)
• Consequence: CCND3 NM_001760.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCND3	NM_001760.5	c.415-42A>T		intron_variant		ENST00000372991.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCND3	ENST00000372991.9	c.415-42A>T		intron_variant		1	NM_001760.5	P1

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122672 AN: 151932 Hom.: 50260 Cov.: 31

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.775

GnomAD3 exomes AF: 0.786 AC: 195697 AN: 249056 Hom.: 77731 AF XY: 0.779 AC XY: 104956 AN XY: 134750

Gnomad AFR exome AF: 0.953

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.655

Gnomad EAS exome AF: 0.910

Gnomad SAS exome AF: 0.822

Gnomad FIN exome AF: 0.755

Gnomad NFE exome AF: 0.727

Gnomad OTH exome AF: 0.755

GnomAD4 exome AF: 0.754 AC: 1099941 AN: 1458540 Hom.: 417143 Cov.: 35 AF XY: 0.755 AC XY: 547346 AN XY: 725150

Gnomad4 AFR exome AF: 0.956

Gnomad4 AMR exome AF: 0.859

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.912

Gnomad4 SAS exome AF: 0.821

Gnomad4 FIN exome AF: 0.758

Gnomad4 NFE exome AF: 0.735

Gnomad4 OTH exome AF: 0.758

GnomAD4 genome AF: 0.808 AC: 122794 AN: 152050 Hom.: 50320 Cov.: 31 AF XY: 0.812 AC XY: 60321 AN XY: 74324

Gnomad4 AFR AF: 0.950

Gnomad4 AMR AF: 0.819

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.833

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.774

Alfa AF: 0.758 Hom.: 8096

Bravo AF: 0.819

Asia WGS AF: 0.864 AC: 3005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2479717; hg19: chr6-41905174;