6-41935269-T-C

Position:

• chr6-41935269-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001760.5(CCND3):​c.*671A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 233,632 control chromosomes in the GnomAD database, including 69,710 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 0.78 (47424 hom., cov: 34)
  • Exomes 𝑓: 0.74 (22286 hom.)
• Consequence: CCND3 NM_001760.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCND3	NM_001760.5	c.*671A>G		3_prime_UTR_variant	5/5	ENST00000372991.9	NP_001751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCND3	ENST00000372991.9	c.*671A>G		3_prime_UTR_variant	5/5	1	NM_001760.5	ENSP00000362082	P1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 119077 AN: 152144 Hom.: 47370 Cov.: 34

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.738 AC: 60051 AN: 81370 Hom.: 22286 Cov.: 0 AF XY: 0.738 AC XY: 27643 AN XY: 37440

Gnomad4 AFR exome AF: 0.948

Gnomad4 AMR exome AF: 0.705

Gnomad4 ASJ exome AF: 0.672

Gnomad4 EAS exome AF: 0.791

Gnomad4 SAS exome AF: 0.711

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.719

Gnomad4 OTH exome AF: 0.742

GnomAD4 genome AF: 0.783 AC: 119186 AN: 152262 Hom.: 47424 Cov.: 34 AF XY: 0.782 AC XY: 58242 AN XY: 74456

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.758

Alfa AF: 0.732 Hom.: 13419

Bravo AF: 0.787

Asia WGS AF: 0.753 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9529; hg19: chr6-41903007;