rs11970772

Variant names:

• chr6-41957552-T-A
• rs11970772
• ENST00000372988.8:c.-45-16967A>T

Variant summary

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

The ENST00000372988.8(CCND3):​c.-45-16967A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,114 control chromosomes in the GnomAD database, including 5,254 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 0.25 (5254 hom., cov: 32)
• Consequence: CCND3 ENST00000372988.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 35 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCND3	NM_001136017.3	c.-45-16967A>T		intron_variant	Intron 1 of 4		NP_001129489.1
CCND3	NM_001424053.1	c.-45-16967A>T		intron_variant	Intron 1 of 4		NP_001410982.1
CCND3	NM_001424055.1	c.-45-16967A>T		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.-45-16967A>T		intron_variant	Intron 1 of 4	1		ENSP00000362079.4
CCND3	ENST00000511642.5	c.-45-16967A>T		intron_variant	Intron 1 of 4	2		ENSP00000426212.1
CCND3	ENST00000510503.5	c.-45-16967A>T		intron_variant	Intron 1 of 3	3		ENSP00000425986.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37923 AN: 151996 Hom.: 5234 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.250 AC: 37983 AN: 152114 Hom.: 5254 Cov.: 32 AF XY: 0.257 AC XY: 19132 AN XY: 74350

African (AFR) AF: 0.256 AC: 10607 AN: 41508

American (AMR) AF: 0.317 AC: 4835 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3472

East Asian (EAS) AF: 0.450 AC: 2325 AN: 5166

South Asian (SAS) AF: 0.475 AC: 2293 AN: 4826

European-Finnish (FIN) AF: 0.238 AC: 2509 AN: 10564

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14256 AN: 67986

Other (OTH) AF: 0.240 AC: 507 AN: 2112

Alfa AF: 0.227 Hom.: 2361

Bravo AF: 0.255

Asia WGS AF: 0.442 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.41
DANN	Benign	0.35
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11970772; hg19: chr6-41925290;