rs3218086

Positions:

• chr6-41942326-C-T

Variant summary

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

The ENST00000372988.8(CCND3):​c.-45-1741G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,126 control chromosomes in the GnomAD database, including 2,977 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 (2977 hom., cov: 31)
• Consequence: CCND3 ENST00000372988.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514

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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND3	NM_001136017.3	c.-45-1741G>A		intron_variant			NP_001129489.1
CCND3	NM_001136126.3	c.-174-4932G>A		intron_variant			NP_001129598.1
CCND3	NM_001287434.2	c.-174-4932G>A		intron_variant			NP_001274363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND3	ENST00000372988.8	c.-45-1741G>A		intron_variant		1		ENSP00000362079
CCND3	ENST00000415497.6	c.-174-4932G>A		intron_variant		2		ENSP00000401595
CCND3	ENST00000502771.1	c.-45-1741G>A		intron_variant		4		ENSP00000425334

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27602 AN: 152008 Hom.: 2965 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.182 AC: 27629 AN: 152126 Hom.: 2977 Cov.: 31 AF XY: 0.190 AC XY: 14106 AN XY: 74350

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.0968

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.175

Alfa AF: 0.178 Hom.: 1978

Bravo AF: 0.184

Asia WGS AF: 0.347 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.8
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3218086; hg19: chr6-41910064;