11-69650913-A-G

Variant names:

• chr11-69650913-A-G
• rs2510467
• NM_053056.3:c.724-205A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_053056.3(CCND1):​c.724-205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,918 control chromosomes in the GnomAD database, including 33,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.65 (33366 hom., cov: 31)
• Consequence: CCND1 NM_053056.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.21
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-69650913-A-G is Benign according to our data. Variant chr11-69650913-A-G is described in ClinVar as Benign. ClinVar VariationId is 1241350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND1	NM_053056.3	MANE Select	c.724-205A>G		intron	N/A	NP_444284.1	P24385

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCND1	ENST00000227507.3	TSL:1 MANE Select	c.724-205A>G		intron	N/A	ENSP00000227507.2	P24385
	CCND1	ENST00000542367.1	TSL:1	n.187-205A>G		intron	N/A
	CCND1	ENST00000913508.1		c.508-205A>G		intron	N/A	ENSP00000583567.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99168 AN: 151800 Hom.: 33327 Cov.: 31

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.653 AC: 99260 AN: 151918 Hom.: 33366 Cov.: 31 AF XY: 0.654 AC XY: 48568 AN XY: 74248

African (AFR) AF: 0.806 AC: 33402 AN: 41454

American (AMR) AF: 0.555 AC: 8472 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1858 AN: 3466

East Asian (EAS) AF: 0.887 AC: 4567 AN: 5146

South Asian (SAS) AF: 0.687 AC: 3297 AN: 4798

European-Finnish (FIN) AF: 0.579 AC: 6117 AN: 10566

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39409 AN: 67910

Other (OTH) AF: 0.663 AC: 1401 AN: 2112

Alfa AF: 0.595 Hom.: 17702

Bravo AF: 0.656

Asia WGS AF: 0.774 AC: 2687 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.44
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs2510467; hg19: chr11-69465681;