rs3218097

Variant names:

• chr6-41937537-G-A
• rs3218097
• NM_001760.5:c.415-143C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-41937537-G-A
• chr6-41937537-G-C
• chr6-41937537-G-T

Variant summary

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

The NM_001760.5(CCND3):​c.415-143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 920,002 control chromosomes in the GnomAD database, including 25,658 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 (3369 hom., cov: 32)
  • Exomes 𝑓: 0.23 (22289 hom.)
• Consequence: CCND3 NM_001760.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585
• Publications: 45 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=-0.86).
• 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.415-143C>T		intron	N/A	NP_001751.1	P30281-1
	CCND3	NM_001424052.1		c.625-143C>T		intron	N/A	NP_001410981.1
	CCND3	NM_001287427.2		c.265-143C>T		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.415-143C>T		intron	N/A	ENSP00000362082.5	P30281-1
	CCND3	ENST00000372988.8	TSL:1	c.172-143C>T		intron	N/A	ENSP00000362079.4	P30281-2
	CCND3	ENST00000372987.8	TSL:2	c.265-143C>T		intron	N/A	ENSP00000362078.4	Q5T8J1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29823 AN: 152026 Hom.: 3366 Cov.: 32

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.179

GnomAD4 exome AF: 0.232 AC: 177983 AN: 767858 Hom.: 22289 AF XY: 0.230 AC XY: 90047 AN XY: 391006

African (AFR) AF: 0.0821 AC: 1547 AN: 18852

American (AMR) AF: 0.128 AC: 2927 AN: 22812

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 4188 AN: 16272

East Asian (EAS) AF: 0.220 AC: 7236 AN: 32858

South Asian (SAS) AF: 0.154 AC: 8396 AN: 54688

European-Finnish (FIN) AF: 0.237 AC: 7750 AN: 32718

Middle Eastern (MID) AF: 0.160 AC: 418 AN: 2614

European-Non Finnish (NFE) AF: 0.249 AC: 137192 AN: 550470

Other (OTH) AF: 0.228 AC: 8329 AN: 36574

GnomAD4 genome AF: 0.196 AC: 29828 AN: 152144 Hom.: 3369 Cov.: 32 AF XY: 0.195 AC XY: 14481 AN XY: 74378

African (AFR) AF: 0.0920 AC: 3821 AN: 41514

American (AMR) AF: 0.159 AC: 2432 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3470

East Asian (EAS) AF: 0.269 AC: 1393 AN: 5174

South Asian (SAS) AF: 0.161 AC: 778 AN: 4824

European-Finnish (FIN) AF: 0.236 AC: 2494 AN: 10588

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17337 AN: 67984

Other (OTH) AF: 0.180 AC: 381 AN: 2112

Alfa AF: 0.233 Hom.: 14985

Bravo AF: 0.186

Asia WGS AF: 0.173 AC: 599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.62
PhyloP100		-0.58
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: rs3218097; hg19: chr6-41905275; COSMIC: COSV107216619; COSMIC: COSV107216619;