11-69650025-G-A

Variant names:

• chr11-69650025-G-A
• rs649392
• NM_053056.3:c.724-1093G>A

Variant summary

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

The NM_053056.3(CCND1):​c.724-1093G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 152,038 control chromosomes in the GnomAD database, including 20,906 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 0.51 (20906 hom., cov: 33)
• Consequence: CCND1 NM_053056.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 28 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 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.724-1093G>A		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.724-1093G>A		intron	N/A	ENSP00000227507.2
	CCND1	ENST00000542367.1	TSL:1	n.187-1093G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78200 AN: 151920 Hom.: 20909 Cov.: 33

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.514 AC: 78215 AN: 152038 Hom.: 20906 Cov.: 33 AF XY: 0.518 AC XY: 38526 AN XY: 74326

African (AFR) AF: 0.386 AC: 15988 AN: 41448

American (AMR) AF: 0.484 AC: 7395 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1764 AN: 3468

East Asian (EAS) AF: 0.877 AC: 4537 AN: 5176

South Asian (SAS) AF: 0.576 AC: 2778 AN: 4824

European-Finnish (FIN) AF: 0.580 AC: 6129 AN: 10560

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37794 AN: 67962

Other (OTH) AF: 0.534 AC: 1127 AN: 2110

Alfa AF: 0.546 Hom.: 46015

Bravo AF: 0.504

Asia WGS AF: 0.661 AC: 2298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.056
DANN	Benign	0.62
PhyloP100		-1.7
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: rs649392; hg19: chr11-69464793;