rs3176459

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_078626.3(CDKN2C):​c.129+1078A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,128 control chromosomes in the GnomAD database, including 7,496 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7496 hom., cov: 33)

Consequence

CDKN2C
NM_078626.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.908
Variant links:
Genes affected
CDKN2C (HGNC:1789): (cyclin dependent kinase inhibitor 2C) The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown to interact with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. Ectopic expression of this gene was shown to suppress the growth of human cells in a manner that appears to correlate with the presence of a wild-type RB1 function. Studies in the knockout mice suggested the roles of this gene in regulating spermatogenesis, as well as in suppressing tumorigenesis. Two alternatively spliced transcript variants of this gene, which encode an identical protein, have been reported. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDKN2CNM_078626.3 linkuse as main transcriptc.129+1078A>G intron_variant ENST00000371761.4
CDKN2CNM_001262.3 linkuse as main transcriptc.129+1078A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDKN2CENST00000371761.4 linkuse as main transcriptc.129+1078A>G intron_variant 1 NM_078626.3 P1
CDKN2CENST00000396148.2 linkuse as main transcriptc.129+1078A>G intron_variant 1 P1
CDKN2CENST00000262662.5 linkuse as main transcriptc.129+1078A>G intron_variant 2 P1

Frequencies

GnomAD3 genomes
AF:
0.307
AC:
46695
AN:
152010
Hom.:
7483
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.301
Gnomad AMI
AF:
0.383
Gnomad AMR
AF:
0.296
Gnomad ASJ
AF:
0.417
Gnomad EAS
AF:
0.0756
Gnomad SAS
AF:
0.287
Gnomad FIN
AF:
0.205
Gnomad MID
AF:
0.509
Gnomad NFE
AF:
0.340
Gnomad OTH
AF:
0.361
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.307
AC:
46735
AN:
152128
Hom.:
7496
Cov.:
33
AF XY:
0.301
AC XY:
22380
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.301
Gnomad4 AMR
AF:
0.295
Gnomad4 ASJ
AF:
0.417
Gnomad4 EAS
AF:
0.0756
Gnomad4 SAS
AF:
0.288
Gnomad4 FIN
AF:
0.205
Gnomad4 NFE
AF:
0.340
Gnomad4 OTH
AF:
0.362
Alfa
AF:
0.324
Hom.:
1945
Bravo
AF:
0.312
Asia WGS
AF:
0.191
AC:
659
AN:
3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
11
DANN
Benign
0.67

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs3176459; hg19: chr1-51437247; API