rs878853637

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001122630.2(CDKN1C):​c.567_590delAGCCCCGGCCCCGGCCCCGGCCCC​(p.Ala190_Pro197del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000803 in 793,628 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P189P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00090 ( 0 hom. )

Consequence

CDKN1C
NM_001122630.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 1.91
Variant links:
Genes affected
CDKN1C (HGNC:1786): (cyclin dependent kinase inhibitor 1C) This gene is imprinted, with preferential expression of the maternal allele. The encoded protein is a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations in this gene are implicated in sporadic cancers and Beckwith-Wiedemann syndorome, suggesting that this gene is a tumor suppressor candidate. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6
Variant 11-2884866-CGGGGCCGGGGCCGGGGCCGGGGCT-C is Benign according to our data. Variant chr11-2884866-CGGGGCCGGGGCCGGGGCCGGGGCT-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 236963.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=1}.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000308 (41/133260) while in subpopulation NFE AF = 0.000519 (31/59782). AF 95% confidence interval is 0.000375. There are 0 homozygotes in GnomAd4. There are 21 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDKN1CNM_001122630.2 linkc.567_590delAGCCCCGGCCCCGGCCCCGGCCCC p.Ala190_Pro197del disruptive_inframe_deletion Exon 2 of 4 ENST00000440480.8 NP_001116102.1 P49918-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDKN1CENST00000440480.8 linkc.567_590delAGCCCCGGCCCCGGCCCCGGCCCC p.Ala190_Pro197del disruptive_inframe_deletion Exon 2 of 4 1 NM_001122630.2 ENSP00000411257.2 P49918-2

Frequencies

GnomAD3 genomes
AF:
0.000308
AC:
41
AN:
133260
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000159
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000216
Gnomad SAS
AF:
0.000465
Gnomad FIN
AF:
0.000128
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000519
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000903
AC:
596
AN:
660368
Hom.:
0
AF XY:
0.000888
AC XY:
276
AN XY:
310650
show subpopulations
African (AFR)
AF:
0.000235
AC:
3
AN:
12772
American (AMR)
AF:
0.00
AC:
0
AN:
1770
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
5206
East Asian (EAS)
AF:
0.000167
AC:
1
AN:
5982
South Asian (SAS)
AF:
0.000145
AC:
2
AN:
13834
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
4614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1438
European-Non Finnish (NFE)
AF:
0.000954
AC:
565
AN:
592082
Other (OTH)
AF:
0.00110
AC:
25
AN:
22670
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.477
Heterozygous variant carriers
0
28
56
83
111
139
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
26
52
78
104
130
<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:
0.000308
AC:
41
AN:
133260
Hom.:
0
Cov.:
32
AF XY:
0.000324
AC XY:
21
AN XY:
64878
show subpopulations
African (AFR)
AF:
0.000159
AC:
6
AN:
37814
American (AMR)
AF:
0.00
AC:
0
AN:
12832
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3164
East Asian (EAS)
AF:
0.000216
AC:
1
AN:
4632
South Asian (SAS)
AF:
0.000465
AC:
2
AN:
4304
European-Finnish (FIN)
AF:
0.000128
AC:
1
AN:
7836
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
250
European-Non Finnish (NFE)
AF:
0.000519
AC:
31
AN:
59782
Other (OTH)
AF:
0.00
AC:
0
AN:
1824
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
2
4
5
7
9
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000506
Hom.:
0

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:1
Jan 20, 2022
Revvity Omics, Revvity
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Sep 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

CDKN1C: BS1 -

Beckwith-Wiedemann syndrome Benign:2
Jan 07, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jun 28, 2021
Sema4, Sema4
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:curation

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.9
Mutation Taster
=191/9
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs878853637; hg19: chr11-2906096; API