6-41940117-G-C

Position:

• chr6-41940117-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001760.5(CCND3):​c.414+253C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,140 control chromosomes in the GnomAD database, including 3,228 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 0.18 (3228 hom., cov: 32)
• Consequence: CCND3 NM_001760.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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]

CCND3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• 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	Protein	UniProt
CCND3	NM_001760.5	c.414+253C>G		intron_variant		ENST00000372991.9	NP_001751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND3	ENST00000372991.9	c.414+253C>G		intron_variant		1	NM_001760.5	ENSP00000362082.5

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28003 AN: 152022 Hom.: 3225 Cov.: 32

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.184 AC: 28008 AN: 152140 Hom.: 3228 Cov.: 32 AF XY: 0.183 AC XY: 13648 AN XY: 74386

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.172

Alfa AF: 0.130 Hom.: 247

Bravo AF: 0.172

Asia WGS AF: 0.170 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.86

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: rs1410492; hg19: chr6-41907855;