chr6-41943447-A-G

Variant names:

• chr6-41943447-A-G
• rs9381100
• ENST00000372988.8:c.-45-2862T>C

Variant summary

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

The ENST00000372988.8(CCND3):​c.-45-2862T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,120 control chromosomes in the GnomAD database, including 4,799 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 0.25 (4799 hom., cov: 32)
• Consequence: CCND3 ENST00000372988.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND3	NM_001136017.3	c.-45-2862T>C		intron_variant	Intron 1 of 4		NP_001129489.1
CCND3	NM_001424053.1	c.-45-2862T>C		intron_variant	Intron 1 of 4		NP_001410982.1
CCND3	NM_001424055.1	c.-45-2862T>C		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.-45-2862T>C		intron_variant	Intron 1 of 4	1		ENSP00000362079.4
CCND3	ENST00000511642.5	c.-45-2862T>C		intron_variant	Intron 1 of 4	2		ENSP00000426212.1
CCND3	ENST00000510503.5	c.-45-2862T>C		intron_variant	Intron 1 of 3	3		ENSP00000425986.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37404 AN: 152000 Hom.: 4800 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.246 AC: 37416 AN: 152120 Hom.: 4799 Cov.: 32 AF XY: 0.246 AC XY: 18264 AN XY: 74364

African (AFR) AF: 0.284 AC: 11764 AN: 41486

American (AMR) AF: 0.194 AC: 2967 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 713 AN: 3462

East Asian (EAS) AF: 0.181 AC: 937 AN: 5186

South Asian (SAS) AF: 0.151 AC: 728 AN: 4826

European-Finnish (FIN) AF: 0.267 AC: 2813 AN: 10554

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16657 AN: 67992

Other (OTH) AF: 0.264 AC: 559 AN: 2116

Alfa AF: 0.242 Hom.: 3677

Bravo AF: 0.244

Asia WGS AF: 0.191 AC: 662 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.73
PhyloP100		0.085
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: rs9381100; hg19: chr6-41911185;