rs13340461

Positions:

• chr6-41956540-C-T

Variant summary

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

The ENST00000372988.8(CCND3):​c.-45-15955G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,022 control chromosomes in the GnomAD database, including 4,422 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 0.23 (4422 hom., cov: 32)
• Consequence: CCND3 ENST00000372988.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCND3	NM_001136017.3	c.-45-15955G>A		intron_variant
CCND3	NM_001136126.3	c.-174-19146G>A		intron_variant
CCND3	NM_001287434.2	c.-174-19146G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCND3	ENST00000372988.8	c.-45-15955G>A		intron_variant		1
CCND3	ENST00000415497.6	c.-174-19146G>A		intron_variant		2
CCND3	ENST00000502771.1	c.-45-15955G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35103 AN: 151902 Hom.: 4422 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.231 AC: 35111 AN: 152022 Hom.: 4422 Cov.: 32 AF XY: 0.226 AC XY: 16760 AN XY: 74290

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.262

Alfa AF: 0.273 Hom.: 3795

Bravo AF: 0.222

Asia WGS AF: 0.181 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.7
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13340461; hg19: chr6-41924278;