6-41942441-G-T

Variant names:

• chr6-41942441-G-T
• rs3218085
• ENST00000372988.8:c.-45-1856C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000372988.8(CCND3):​c.-45-1856C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00846 in 152,284 control chromosomes in the GnomAD database, including 8 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 0.0085 (8 hom., cov: 31)
• Consequence: CCND3 ENST00000372988.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.376
• Publications: 3 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High AC in GnomAd4 at 1288 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND3	NM_001136017.3	c.-45-1856C>A		intron_variant	Intron 1 of 4		NP_001129489.1
CCND3	NM_001424053.1	c.-45-1856C>A		intron_variant	Intron 1 of 4		NP_001410982.1
CCND3	NM_001424055.1	c.-45-1856C>A		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.-45-1856C>A		intron_variant	Intron 1 of 4	1		ENSP00000362079.4
CCND3	ENST00000511642.5	c.-45-1856C>A		intron_variant	Intron 1 of 4	2		ENSP00000426212.1
CCND3	ENST00000510503.5	c.-45-1856C>A		intron_variant	Intron 1 of 3	3		ENSP00000425986.1

Frequencies

GnomAD3 genomes AF: 0.00846 AC: 1287 AN: 152166 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0164

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.00768

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

GnomAD4 genome AF: 0.00846 AC: 1288 AN: 152284 Hom.: 8 Cov.: 31 AF XY: 0.00850 AC XY: 633 AN XY: 74460

African (AFR) AF: 0.00176 AC: 73 AN: 41566

American (AMR) AF: 0.00889 AC: 136 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

European-Finnish (FIN) AF: 0.0164 AC: 174 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0126 AC: 860 AN: 68026

Other (OTH) AF: 0.00807 AC: 17 AN: 2106

Alfa AF: 0.0136 Hom.: 4

Bravo AF: 0.00699

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.3
DANN	Benign	0.84
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3218085; hg19: chr6-41910179;