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rs9344

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_053056.3(CCND1):c.723G>A(p.Pro241=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.444 in 1,613,168 control chromosomes in the GnomAD database, including 162,210 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as 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

2
Splicing: ADA: 0.4188
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:3

Conservation

PhyloP100: 5.13
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 11-69648142-G-A is Benign according to our data. Variant chr11-69648142-G-A is described in ClinVar as [Benign]. Clinvar id is 13755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-69648142-G-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCND1NM_053056.3 linkuse as main transcriptc.723G>A p.Pro241= splice_region_variant, synonymous_variant 4/5 ENST00000227507.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCND1ENST00000227507.3 linkuse as main transcriptc.723G>A p.Pro241= splice_region_variant, synonymous_variant 4/51 NM_053056.3 P1
CCND1ENST00000542367.1 linkuse as main transcriptn.186G>A splice_region_variant, non_coding_transcript_exon_variant 1/21
CCND1ENST00000536559.1 linkuse as main transcriptc.*143G>A 3_prime_UTR_variant 2/23
CCND1ENST00000545484.1 linkuse as main transcriptn.429G>A non_coding_transcript_exon_variant 2/25

Frequencies

GnomAD3 genomes
AF:
0.393
AC:
59681
AN:
152010
Hom.:
12647
Cov.:
33
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
GnomAD3 exomes
AF:
0.453
AC:
113515
AN:
250702
Hom.:
26634
AF XY:
0.464
AC XY:
62937
AN XY:
135576
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 SAS exome
AF:
0.522
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.:
43
AF XY:
0.454
AC XY:
329998
AN XY:
726820
show subpopulations
Gnomad4 AFR exome
AF:
0.215
Gnomad4 AMR exome
AF:
0.379
Gnomad4 ASJ exome
AF:
0.444
Gnomad4 EAS exome
AF:
0.523
Gnomad4 SAS exome
AF:
0.523
Gnomad4 FIN exome
AF:
0.481
Gnomad4 NFE exome
AF:
0.449
Gnomad4 OTH exome
AF:
0.455
GnomAD4 genome
AF:
0.392
AC:
59681
AN:
152128
Hom.:
12635
Cov.:
33
AF XY:
0.396
AC XY:
29472
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.219
Gnomad4 AMR
AF:
0.403
Gnomad4 ASJ
AF:
0.446
Gnomad4 EAS
AF:
0.547
Gnomad4 SAS
AF:
0.524
Gnomad4 FIN
AF:
0.470
Gnomad4 NFE
AF:
0.458
Gnomad4 OTH
AF:
0.429
Alfa
AF:
0.449
Hom.:
21060
Bravo
AF:
0.380
Asia WGS
AF:
0.508
AC:
1766
AN:
3478
EpiCase
AF:
0.470
EpiControl
AF:
0.469

ClinVar

Significance: Benign
Submissions summary: Benign:2Other:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

CCND1-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxApr 16, 2020This variant is associated with the following publications: (PMID: 26617896, 25997217, 16783567, 21268129, 11896626, 7675441, 10667569, 20680537, 22606291, 23502783, 21594903, 21161398, 24270739, 21107342, 17308274, 17960397, 11418364, 22304571, 20380574, 18843022, 22901215, 21273603) -
MULTIPLE MYELOMA, t(11;14) TYPE, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMay 01, 2013- -
Colorectal cancer, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMay 01, 2013- -
VON HIPPEL-LINDAU SYNDROME, MODIFIER OF Other:1
risk factor, no assertion criteria providedliterature onlyOMIMMay 01, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
18
Dann
Benign
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9344; hg19: chr11-69462910; COSMIC: COSV57118864; COSMIC: COSV57118864; API