rs3218085

chr6-41942441-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000372988.8(CCND3):c.-45-1856C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00846 in 152,284 control chromosomes in the GnomAD database, including 8 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 0.0085 (8 hom., cov: 31)
• Consequence: CCND3 ENST00000372988.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High AC in GnomAd at 1287 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCND3	NM_001136017.3	c.-45-1856C>A		intron_variant
CCND3	NM_001136126.3	c.-174-5047C>A		intron_variant
CCND3	NM_001287434.2	c.-174-5047C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCND3	ENST00000372988.8	c.-45-1856C>A		intron_variant		1
CCND3	ENST00000415497.6	c.-174-5047C>A		intron_variant		2
CCND3	ENST00000502771.1	c.-45-1856C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00846 AC: 1287 AN: 152166 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.00768

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

GnomAD4 genome AF: 0.00846 AC: 1288 AN: 152284 Hom.: 8 Cov.: 31 AF XY: 0.00850 AC XY: 633 AN XY: 74460

Gnomad4 AFR AF: 0.00176

Gnomad4 AMR AF: 0.00889

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0164

Gnomad4 NFE AF: 0.0126

Gnomad4 OTH AF: 0.00807

Alfa AF: 0.0136 Hom.: 4

Bravo AF: 0.00699

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.3
Dann	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3218085; hg19: chr6-41910179;