rs9349204

Variant names:

• chr6-41946640-A-G
• rs9349204
• ENST00000372988.8:c.-45-6055T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-41946640-A-G
• chr6-41946640-A-T

Variant summary

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

The ENST00000372988.8(CCND3):​c.-45-6055T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 146,576 control chromosomes in the GnomAD database, including 4,192 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 0.23 (4192 hom., cov: 26)
• Consequence: CCND3 ENST00000372988.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• Publications: 28 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=-1.07).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND3	NM_001136017.3	c.-45-6055T>C		intron_variant	Intron 1 of 4		NP_001129489.1
CCND3	NM_001424053.1	c.-45-6055T>C		intron_variant	Intron 1 of 4		NP_001410982.1
CCND3	NM_001424055.1	c.-45-6055T>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.-45-6055T>C		intron_variant	Intron 1 of 4	1		ENSP00000362079.4
CCND3	ENST00000511642.5	c.-45-6055T>C		intron_variant	Intron 1 of 4	2		ENSP00000426212.1
CCND3	ENST00000510503.5	c.-45-6055T>C		intron_variant	Intron 1 of 3	3		ENSP00000425986.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 33473 AN: 146490 Hom.: 4188 Cov.: 26

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.228 AC: 33484 AN: 146576 Hom.: 4192 Cov.: 26 AF XY: 0.224 AC XY: 15896 AN XY: 70940

African (AFR) AF: 0.170 AC: 6760 AN: 39820

American (AMR) AF: 0.168 AC: 2413 AN: 14388

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 946 AN: 3440

East Asian (EAS) AF: 0.334 AC: 1657 AN: 4960

South Asian (SAS) AF: 0.190 AC: 888 AN: 4668

European-Finnish (FIN) AF: 0.227 AC: 2058 AN: 9082

Middle Eastern (MID) AF: 0.195 AC: 55 AN: 282

European-Non Finnish (NFE) AF: 0.269 AC: 18038 AN: 67032

Other (OTH) AF: 0.214 AC: 430 AN: 2008

Alfa AF: 0.248 Hom.: 8308

Bravo AF: 0.226

Asia WGS AF: 0.223 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.0
DANN	Benign	0.40
PhyloP100		-0.76
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: rs9349204; hg19: chr6-41914378;