rs602652

Variant names:

• chr11-69647874-G-A
• rs602652
• NM_053056.3:c.575-120G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-69647874-G-A
• chr11-69647874-G-C
• chr11-69647874-G-T

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.575-120G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,112,970 control chromosomes in the GnomAD database, including 129,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15197 hom., cov: 33)
  • Exomes 𝑓: 0.48 (114324 hom.)
• Consequence: CCND1 NM_053056.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.811
• Publications: 16 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=-0.88).
• BP6: Variant 11-69647874-G-A is Benign according to our data. Variant chr11-69647874-G-A is described in ClinVar as Benign. ClinVar VariationId is 1227388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 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.575-120G>A		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.575-120G>A		intron	N/A	ENSP00000227507.2	P24385
	CCND1	ENST00000913508.1		c.359-120G>A		intron	N/A	ENSP00000583567.1
	CCND1	ENST00000536559.1	TSL:3	c.199-120G>A		intron	N/A	ENSP00000438482.1	F5H437

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65835 AN: 151856 Hom.: 15201 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.456

GnomAD4 exome AF: 0.480 AC: 461733 AN: 960996 Hom.: 114324 AF XY: 0.485 AC XY: 235666 AN XY: 485704

African (AFR) AF: 0.290 AC: 6663 AN: 22946

American (AMR) AF: 0.390 AC: 12190 AN: 31224

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 8143 AN: 18174

East Asian (EAS) AF: 0.806 AC: 29061 AN: 36036

South Asian (SAS) AF: 0.553 AC: 34769 AN: 62868

European-Finnish (FIN) AF: 0.518 AC: 17932 AN: 34616

Middle Eastern (MID) AF: 0.533 AC: 1727 AN: 3240

European-Non Finnish (NFE) AF: 0.466 AC: 329896 AN: 708604

Other (OTH) AF: 0.493 AC: 21352 AN: 43288

GnomAD4 genome AF: 0.433 AC: 65855 AN: 151974 Hom.: 15197 Cov.: 33 AF XY: 0.439 AC XY: 32594 AN XY: 74266

African (AFR) AF: 0.290 AC: 12025 AN: 41442

American (AMR) AF: 0.417 AC: 6368 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3466

East Asian (EAS) AF: 0.816 AC: 4191 AN: 5136

South Asian (SAS) AF: 0.560 AC: 2695 AN: 4814

European-Finnish (FIN) AF: 0.507 AC: 5361 AN: 10574

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.474 AC: 32173 AN: 67938

Other (OTH) AF: 0.457 AC: 965 AN: 2112

Alfa AF: 0.455 Hom.: 5512

Bravo AF: 0.422

Asia WGS AF: 0.619 AC: 2150 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	1.3
DANN	Benign	0.57
PhyloP100		-0.81
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: rs602652; hg19: chr11-69462642; COSMIC: COSV57122897; COSMIC: COSV57122897;