ENST00000372988.8:c.-46+53568C>T

Variant names:

• chr6-41994933-G-A
• rs9357377
• ENST00000372988.8:c.-46+53568C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000372988.8(CCND3):​c.-46+53568C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 151,826 control chromosomes in the GnomAD database, including 1,900 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 0.16 (1900 hom., cov: 30)
• Consequence: CCND3 ENST00000372988.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND3	NM_001136017.3	c.-46+53568C>T		intron_variant	Intron 1 of 4		NP_001129489.1
CCND3	NM_001424053.1	c.-45-54348C>T		intron_variant	Intron 1 of 4		NP_001410982.1
CCND3	NM_001424055.1	c.-46+35076C>T		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.-46+53568C>T		intron_variant	Intron 1 of 4	1		ENSP00000362079.4
CCND3	ENST00000511642.5	c.-45-54348C>T		intron_variant	Intron 1 of 4	2		ENSP00000426212.1
CCND3	ENST00000510503.5	c.-46+53568C>T		intron_variant	Intron 1 of 3	3		ENSP00000425986.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23529 AN: 151708 Hom.: 1901 Cov.: 30

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.155 AC: 23535 AN: 151826 Hom.: 1900 Cov.: 30 AF XY: 0.154 AC XY: 11434 AN XY: 74190

African (AFR) AF: 0.125 AC: 5155 AN: 41402

American (AMR) AF: 0.176 AC: 2681 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3470

East Asian (EAS) AF: 0.183 AC: 938 AN: 5130

South Asian (SAS) AF: 0.128 AC: 613 AN: 4804

European-Finnish (FIN) AF: 0.151 AC: 1593 AN: 10520

Middle Eastern (MID) AF: 0.159 AC: 46 AN: 290

European-Non Finnish (NFE) AF: 0.168 AC: 11437 AN: 67952

Other (OTH) AF: 0.176 AC: 371 AN: 2112

Alfa AF: 0.0826 Hom.: 109

Bravo AF: 0.156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.4
DANN	Benign	0.85
PhyloP100		0.47
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: rs9357377; hg19: chr6-41962671;