chr6-41938923-A-G

Variant names:

• chr6-41938923-A-G
• rs3218092
• NM_001760.5:c.414+1447T>C

Variant summary

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

The NM_001424056.1(CCND3):​c.-932T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,522 control chromosomes in the GnomAD database, including 3,040 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 0.18 (3040 hom., cov: 31)
• Consequence: CCND3 NM_001424056.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880
• 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 (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424056.1. 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_001760.5	MANE Select	c.414+1447T>C		intron	N/A	NP_001751.1	P30281-1
	CCND3	NM_001424056.1		c.-932T>C		5_prime_UTR	Exon 1 of 4	NP_001410985.1	P30281-4
	CCND3	NM_001424052.1		c.624+1447T>C		intron	N/A	NP_001410981.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND3	ENST00000372991.9	TSL:1 MANE Select	c.414+1447T>C		intron	N/A	ENSP00000362082.5	P30281-1
	CCND3	ENST00000372988.8	TSL:1	c.171+1447T>C		intron	N/A	ENSP00000362079.4	P30281-2
	CCND3	ENST00000372987.8	TSL:2	c.264+1447T>C		intron	N/A	ENSP00000362078.4	Q5T8J1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 27950 AN: 151404 Hom.: 3027 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.0961

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.185 AC: 27976 AN: 151522 Hom.: 3040 Cov.: 31 AF XY: 0.192 AC XY: 14227 AN XY: 73996

African (AFR) AF: 0.110 AC: 4521 AN: 41282

American (AMR) AF: 0.279 AC: 4241 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.0961 AC: 333 AN: 3466

East Asian (EAS) AF: 0.390 AC: 2001 AN: 5134

South Asian (SAS) AF: 0.377 AC: 1807 AN: 4794

European-Finnish (FIN) AF: 0.204 AC: 2139 AN: 10486

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12342 AN: 67844

Other (OTH) AF: 0.179 AC: 377 AN: 2106

Alfa AF: 0.181 Hom.: 358

Bravo AF: 0.187

Asia WGS AF: 0.346 AC: 1208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.46
DANN	Benign	0.33
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3218092; hg19: chr6-41906661; COSMIC: COSV65912652; COSMIC: COSV65912652;