rs13340461

Variant names:

• chr6-41956540-C-T
• rs13340461
• ENST00000372988.8:c.-45-15955G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCND3	NM_001136017.3	c.-45-15955G>A		intron_variant	Intron 1 of 4		NP_001129489.1
CCND3	NM_001424053.1	c.-45-15955G>A		intron_variant	Intron 1 of 4		NP_001410982.1
CCND3	NM_001424055.1	c.-45-15955G>A		intron_variant	Intron 2 of 5		NP_001410984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCND3	ENST00000372988.8	c.-45-15955G>A		intron_variant	Intron 1 of 4	1		ENSP00000362079.4
CCND3	ENST00000511642.5	c.-45-15955G>A		intron_variant	Intron 1 of 4	2		ENSP00000426212.1
CCND3	ENST00000510503.5	c.-45-15955G>A		intron_variant	Intron 1 of 3	3		ENSP00000425986.1

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

African (AFR) AF: 0.142 AC: 5887 AN: 41500

American (AMR) AF: 0.202 AC: 3089 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3472

East Asian (EAS) AF: 0.158 AC: 818 AN: 5164

South Asian (SAS) AF: 0.190 AC: 916 AN: 4818

European-Finnish (FIN) AF: 0.270 AC: 2840 AN: 10522

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19400 AN: 67964

Other (OTH) AF: 0.262 AC: 553 AN: 2108

Alfa AF: 0.275 Hom.: 5345

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
PhyloP100		0.096
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs13340461; hg19: chr6-41924278;