rs9344
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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. 3/3 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
NM_053056.3 splice_region, synonymous
Scores
2
Splicing: ADA: 0.4188
2
Clinical Significance
Conservation
PhyloP100: 5.13
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 |
---|---|---|---|---|---|---|---|
CCND1 | NM_053056.3 | c.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 |
---|---|---|---|---|---|---|---|---|---|
CCND1 | ENST00000227507.3 | c.723G>A | p.Pro241= | splice_region_variant, synonymous_variant | 4/5 | 1 | NM_053056.3 | P1 | |
CCND1 | ENST00000542367.1 | n.186G>A | splice_region_variant, non_coding_transcript_exon_variant | 1/2 | 1 | ||||
CCND1 | ENST00000536559.1 | c.*143G>A | 3_prime_UTR_variant | 2/2 | 3 | ||||
CCND1 | ENST00000545484.1 | n.429G>A | non_coding_transcript_exon_variant | 2/2 | 5 |
Frequencies
GnomAD3 genomes AF: 0.393 AC: 59681AN: 152010Hom.: 12647 Cov.: 33
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GnomAD3 exomes AF: 0.453 AC: 113515AN: 250702Hom.: 26634 AF XY: 0.464 AC XY: 62937AN XY: 135576
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GnomAD4 exome AF: 0.449 AC: 656603AN: 1461040Hom.: 149575 Cov.: 43 AF XY: 0.454 AC XY: 329998AN XY: 726820
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GnomAD4 genome AF: 0.392 AC: 59681AN: 152128Hom.: 12635 Cov.: 33 AF XY: 0.396 AC XY: 29472AN XY: 74368
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ClinVar
Significance: Benign
Submissions summary: Benign:3Other:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 16, 2020 | This 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) - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
CCND1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
MULTIPLE MYELOMA, t(11;14) TYPE, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria provided | literature only | OMIM | May 01, 2013 | - - |
Colorectal cancer, susceptibility to Other:1
risk factor, no assertion criteria provided | literature only | OMIM | May 01, 2013 | - - |
VON HIPPEL-LINDAU SYNDROME, MODIFIER OF Other:1
risk factor, no assertion criteria provided | literature only | OMIM | May 01, 2013 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at