11-69648710-AGG-AG

Variant names:

• chr11-69648710-AG-A
• rs3212879
• NM_053056.3:c.723+571delG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_053056.3(CCND1):​c.723+571delG variant causes a intron change. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (17190 hom., cov: 0)
• Consequence: CCND1 NM_053056.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78
• Publications: 8 publications found

Genes affected

CCND1 (HGNC:1582): (cyclin D1) The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout 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 activity is required for cell cycle G1/S transition. This protein has been shown to interact with tumor suppressor protein Rb and the expression of this gene is regulated positively by Rb. Mutations, amplification and overexpression of this gene, which alters cell cycle progression, are observed frequently in a variety of human cancers. [provided by RefSeq, Dec 2019]

CCND1 Gene-Disease associations (from GenCC):

• von Hippel-Lindau disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053056.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND1	NM_053056.3	MANE Select	c.723+571delG		intron	N/A	NP_444284.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND1	ENST00000227507.3	TSL:1 MANE Select	c.723+569delG		intron	N/A	ENSP00000227507.2
	CCND1	ENST00000542367.1	TSL:1	n.186+569delG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68151 AN: 152018 Hom.: 17198 Cov.: 0

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.448 AC: 68148 AN: 152134 Hom.: 17190 Cov.: 0 AF XY: 0.455 AC XY: 33821 AN XY: 74366

African (AFR) AF: 0.216 AC: 8977 AN: 41518

American (AMR) AF: 0.444 AC: 6790 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1500 AN: 3468

East Asian (EAS) AF: 0.848 AC: 4380 AN: 5164

South Asian (SAS) AF: 0.565 AC: 2729 AN: 4828

European-Finnish (FIN) AF: 0.575 AC: 6083 AN: 10584

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36028 AN: 67954

Other (OTH) AF: 0.472 AC: 998 AN: 2114

Alfa AF: 0.476 Hom.: 2250

Bravo AF: 0.428

Asia WGS AF: 0.622 AC: 2159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3212879; hg19: chr11-69463478;