6-42041593-G-T

Position:

• chr6-42041593-G-T

Variant summary

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

The NM_001136017.3(CCND3):​c.-46+6908C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 152,200 control chromosomes in the GnomAD database, including 346 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 0.051 (346 hom., cov: 32)
• Consequence: CCND3 NM_001136017.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.679

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND3	NM_001136017.3	c.-46+6908C>A		intron_variant			NP_001129489.1
CCND3	NM_001424053.1	c.-46+8058C>A		intron_variant			NP_001410982.1
CCND3	NM_001424055.1	c.-228+6908C>A		intron_variant			NP_001410984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND3	ENST00000372988.8	c.-46+6908C>A		intron_variant		1		ENSP00000362079.4
CCND3	ENST00000511642.5	c.-46+8058C>A		intron_variant		2		ENSP00000426212.1
CCND3	ENST00000510503.5	c.-46+6908C>A		intron_variant		3		ENSP00000425986.1

Frequencies

GnomAD3 genomes AF: 0.0506 AC: 7693 AN: 152082 Hom.: 344 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0645

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0473

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

GnomAD4 genome AF: 0.0507 AC: 7724 AN: 152200 Hom.: 346 Cov.: 32 AF XY: 0.0506 AC XY: 3763 AN XY: 74428

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0525

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0647

Gnomad4 FIN AF: 0.0205

Gnomad4 NFE AF: 0.0187

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0275 Hom.: 27

Bravo AF: 0.0575

Asia WGS AF: 0.133 AC: 463 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	3.7
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4331978; hg19: chr6-42009331;