chr6-41940117-G-C

Variant names:

• chr6-41940117-G-C
• rs1410492
• NM_001760.5:c.414+253C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001760.5(CCND3):​c.414+253C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,140 control chromosomes in the GnomAD database, including 3,228 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 (3228 hom., cov: 32)
• Consequence: CCND3 NM_001760.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND3	NM_001760.5	MANE Select	c.414+253C>G		intron	N/A	NP_001751.1	P30281-1
	CCND3	NM_001424052.1		c.624+253C>G		intron	N/A	NP_001410981.1
	CCND3	NM_001287427.2		c.264+253C>G		intron	N/A	NP_001274356.1	Q5T8J1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND3	ENST00000372991.9	TSL:1 MANE Select	c.414+253C>G		intron	N/A	ENSP00000362082.5	P30281-1
	CCND3	ENST00000372988.8	TSL:1	c.171+253C>G		intron	N/A	ENSP00000362079.4	P30281-2
	CCND3	ENST00000372987.8	TSL:2	c.264+253C>G		intron	N/A	ENSP00000362078.4	Q5T8J1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28003 AN: 152022 Hom.: 3225 Cov.: 32

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.184 AC: 28008 AN: 152140 Hom.: 3228 Cov.: 32 AF XY: 0.183 AC XY: 13648 AN XY: 74386

African (AFR) AF: 0.0521 AC: 2164 AN: 41532

American (AMR) AF: 0.152 AC: 2322 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 900 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1390 AN: 5170

South Asian (SAS) AF: 0.161 AC: 777 AN: 4820

European-Finnish (FIN) AF: 0.235 AC: 2492 AN: 10582

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17310 AN: 67968

Other (OTH) AF: 0.172 AC: 363 AN: 2108

Alfa AF: 0.130 Hom.: 247

Bravo AF: 0.172

Asia WGS AF: 0.170 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		1.1
PromoterAI		-0.094	Neutral
Mutation Taster		=95/5	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: rs1410492; hg19: chr6-41907855;