NM_001760.5:c.*1023G>A

Variant names:

• chr6-41934917-C-T
• rs3218108
• NM_001760.5:c.*1023G>A

Variant summary

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

The NM_001760.5(CCND3):​c.*1023G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 221,392 control chromosomes in the GnomAD database, including 5,349 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 0.20 (3330 hom., cov: 33)
  • Exomes 𝑓: 0.23 (2019 hom.)
• Consequence: CCND3 NM_001760.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 14 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001760.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND3	NM_001760.5	MANE Select	c.*1023G>A		downstream_gene	N/A	NP_001751.1
	CCND3	NM_001424052.1		c.*1023G>A		downstream_gene	N/A	NP_001410981.1
	CCND3	NM_001287427.2		c.*1023G>A		downstream_gene	N/A	NP_001274356.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND3	ENST00000372991.9	TSL:1 MANE Select	c.*1023G>A		downstream_gene	N/A	ENSP00000362082.5
	CCND3	ENST00000372988.8	TSL:1	c.*1023G>A		downstream_gene	N/A	ENSP00000362079.4
	CCND3	ENST00000372987.8	TSL:2	c.*1023G>A		downstream_gene	N/A	ENSP00000362078.4

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29791 AN: 152098 Hom.: 3328 Cov.: 33

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.232 AC: 16071 AN: 69176 Hom.: 2019 Cov.: 0 AF XY: 0.237 AC XY: 7567 AN XY: 31970

African (AFR) AF: 0.0762 AC: 246 AN: 3228

American (AMR) AF: 0.150 AC: 313 AN: 2080

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 1151 AN: 4348

East Asian (EAS) AF: 0.199 AC: 1999 AN: 10052

South Asian (SAS) AF: 0.126 AC: 75 AN: 594

European-Finnish (FIN) AF: 0.140 AC: 7 AN: 50

Middle Eastern (MID) AF: 0.183 AC: 79 AN: 432

European-Non Finnish (NFE) AF: 0.253 AC: 10785 AN: 42612

Other (OTH) AF: 0.245 AC: 1416 AN: 5780

GnomAD4 genome AF: 0.196 AC: 29809 AN: 152216 Hom.: 3330 Cov.: 33 AF XY: 0.195 AC XY: 14526 AN XY: 74416

African (AFR) AF: 0.0875 AC: 3637 AN: 41562

American (AMR) AF: 0.166 AC: 2542 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3468

East Asian (EAS) AF: 0.289 AC: 1496 AN: 5180

South Asian (SAS) AF: 0.157 AC: 757 AN: 4832

European-Finnish (FIN) AF: 0.240 AC: 2534 AN: 10564

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17220 AN: 67994

Other (OTH) AF: 0.193 AC: 407 AN: 2112

Alfa AF: 0.226 Hom.: 7064

Bravo AF: 0.186

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.3
DANN	Benign	0.63
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs3218108; hg19: chr6-41902655;