rs9344

Variant names:

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -15 ACMG points: 0P and 15B. BA1BP4_ModerateBP6_StrongBP7

The NM_053056.3(CCND1):c.723G>A (p.Pro241Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.444 (AC=716,284) in the gnomAD database across 1,613,168 control chromosomes, including 162,210 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.531. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12635 hom., cov: 33)

Exomes 𝑓: 0.45 ( 149575 hom. )

Consequence

CCND1
NM_053056.3 splice_region, synonymous

Scores

Splicing: ADA: 0.4188

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:3

Conservation

PhyloP100: 5.13

Publications

492 publications found

Variant links:

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

CCND1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_053056.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).

BP6

ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).

BP7

Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.5306 — exceeds 5%% threshold (BA1 applied)

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.723G>A	p.Pro241Pro	splice_region synonymous	Exon 4 of 5	NP_444284.1	P24385

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCND1	ENST00000227507.3	TSL:1 MANE Select	c.723G>A	p.Pro241Pro	splice_region synonymous	Exon 4 of 5	ENSP00000227507.2	P24385
CCND1	ENST00000542367.1	TSL:1	n.186G>A		splice_region non_coding_transcript_exon	Exon 1 of 2
CCND1	ENST00000913508.1		c.507G>A	p.Pro169Pro	splice_region synonymous	Exon 3 of 4	ENSP00000583567.1

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59681

AN:

152010

Hom.:

12647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.395

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.429

GnomAD2 exomes

AF:

0.453

AC:

113515

AN:

250702

AF XY:

0.464

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.448

Gnomad EAS exome

AF:

0.569

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.466

Gnomad OTH exome

AF:

0.462

GnomAD4 exome

AF:

0.449

AC:

656603

AN:

1461040

Hom.:

149575

Cov.:

AF XY:

0.454

AC XY:

329998

AN XY:

726820

show subpopulations

African (AFR)

AF:

0.215

AC:

7206

AN:

33470

American (AMR)

AF:

0.379

AC:

16954

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

11599

AN:

26128

East Asian (EAS)

AF:

0.523

AC:

20746

AN:

39688

South Asian (SAS)

AF:

0.523

AC:

45094

AN:

86238

European-Finnish (FIN)

AF:

0.481

AC:

25465

AN:

52966

Middle Eastern (MID)

AF:

0.515

AC:

2968

AN:

5766

European-Non Finnish (NFE)

AF:

0.449

AC:

499080

AN:

1111706

Other (OTH)

AF:

0.455

AC:

27491

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

18898

37797

56695

75594

94492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14898

29796

44694

59592

74490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.392

AC:

59681

AN:

152128

Hom.:

12635

Cov.:

AF XY:

0.396

AC XY:

29472

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.219

AC:

9080

AN:

41524

American (AMR)

AF:

0.403

AC:

6161

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.446

AC:

1549

AN:

3472

East Asian (EAS)

AF:

0.547

AC:

2825

AN:

5160

South Asian (SAS)

AF:

0.524

AC:

2526

AN:

4822

European-Finnish (FIN)

AF:

0.470

AC:

4972

AN:

10580

Middle Eastern (MID)

AF:

0.479

AC:

140

AN:

292

European-Non Finnish (NFE)

AF:

0.458

AC:

31162

AN:

67966

Other (OTH)

AF:

0.429

AC:

906

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1844

3687

5531

7374

9218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

594

1188

1782

2376

2970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.437

Hom.:

52594

Bravo

AF:

0.380

Asia WGS

AF:

0.508

AC:

1766

AN:

3478

EpiCase

AF:

0.470

EpiControl

AF:

0.469

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.483

AC:

59307

AN:

122753

Turkish Variome

AF:

0.521

AC:

3494

AN:

6708

Hom.:

942

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.572

AC:

5124

AN:

8960

Hom.:

1463

ABraOM SABE-WGS-1171

AF:

0.403

AC:

944

AN:

2342

Hom.:

196

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

CCND1-related disorder (1)

Colorectal cancer, susceptibility to (1)

MULTIPLE MYELOMA, t(11;14) TYPE, SUSCEPTIBILITY TO (1)

VON HIPPEL-LINDAU SYNDROME, MODIFIER OF (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Mutation Taster

=56/44

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.42

dbscSNV1_RF

Benign

0.39

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over