rs9349205

Variant names:

• chr6-41957421-G-A
• rs9349205
• ENST00000372988.8:c.-45-16836C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-41957421-G-A
• chr6-41957421-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001136017.3(CCND3):​c.-45-16836C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,138 control chromosomes in the GnomAD database, including 2,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2977 hom., cov: 32)
• Consequence: CCND3 NM_001136017.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.680
• Publications: 43 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 6-41957421-G-A is Benign according to our data. Variant chr6-41957421-G-A is described in ClinVar as Benign. ClinVar VariationId is 1282713.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136017.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND3	NM_001136017.3		c.-45-16836C>T		intron	N/A	NP_001129489.1	P30281-2
	CCND3	NM_001424053.1		c.-45-16836C>T		intron	N/A	NP_001410982.1	P30281-2
	CCND3	NM_001424055.1		c.-45-16836C>T		intron	N/A	NP_001410984.1	P30281-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND3	ENST00000372988.8	TSL:1	c.-45-16836C>T		intron	N/A	ENSP00000362079.4	P30281-2
	CCND3	ENST00000511642.5	TSL:2	c.-45-16836C>T		intron	N/A	ENSP00000426212.1	P30281-2
	CCND3	ENST00000510503.5	TSL:3	c.-45-16836C>T		intron	N/A	ENSP00000425986.1	D6RI00

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26886 AN: 152020 Hom.: 2974 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.177 AC: 26891 AN: 152138 Hom.: 2977 Cov.: 32 AF XY: 0.177 AC XY: 13142 AN XY: 74368

African (AFR) AF: 0.0508 AC: 2108 AN: 41526

American (AMR) AF: 0.145 AC: 2210 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 855 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1395 AN: 5166

South Asian (SAS) AF: 0.167 AC: 803 AN: 4820

European-Finnish (FIN) AF: 0.224 AC: 2362 AN: 10568

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16518 AN: 67998

Other (OTH) AF: 0.168 AC: 355 AN: 2112

Alfa AF: 0.220 Hom.: 13043

Bravo AF: 0.166

Asia WGS AF: 0.171 AC: 594 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.7
DANN	Benign	0.70
PhyloP100		-0.68
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: rs9349205; hg19: chr6-41925159;