1-50974421-C-T

Variant names:

• chr1-50974421-C-T
• rs12855
• NM_078626.3:c.*151C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_078626.3(CDKN2C):​c.*151C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 677,044 control chromosomes in the GnomAD database, including 5,124 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 0.15 (2391 hom., cov: 33)
  • Exomes 𝑓: 0.093 (2733 hom.)
• Consequence: CDKN2C NM_078626.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 30 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078626.3. 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
	CDKN2C	NM_078626.3	MANE Select	c.*151C>T		3_prime_UTR	Exon 2 of 2	NP_523240.1	Q6ICV4
	CDKN2C	NM_001262.3		c.*151C>T		3_prime_UTR	Exon 3 of 3	NP_001253.1	Q6ICV4
	CDKN2C	NM_001429675.1		c.*151C>T		3_prime_UTR	Exon 4 of 4	NP_001416604.1	Q6ICV4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2C	ENST00000371761.4	TSL:1 MANE Select	c.*151C>T		3_prime_UTR	Exon 2 of 2	ENSP00000360826.3	P42773
	CDKN2C	ENST00000396148.2	TSL:1	c.*151C>T		3_prime_UTR	Exon 3 of 3	ENSP00000379452.1	P42773
	CDKN2C	ENST00000262662.5	TSL:2	c.*151C>T		3_prime_UTR	Exon 4 of 4	ENSP00000262662.1	P42773

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22327 AN: 152086 Hom.: 2385 Cov.: 33

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0959

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.0926 AC: 48576 AN: 524840 Hom.: 2733 Cov.: 7 AF XY: 0.0910 AC XY: 24067 AN XY: 264428

African (AFR) AF: 0.307 AC: 4326 AN: 14110

American (AMR) AF: 0.0723 AC: 1006 AN: 13918

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 1815 AN: 13034

East Asian (EAS) AF: 0.0952 AC: 2835 AN: 29780

South Asian (SAS) AF: 0.0557 AC: 1429 AN: 25668

European-Finnish (FIN) AF: 0.0531 AC: 1462 AN: 27512

Middle Eastern (MID) AF: 0.0785 AC: 163 AN: 2076

European-Non Finnish (NFE) AF: 0.0881 AC: 32673 AN: 370960

Other (OTH) AF: 0.103 AC: 2867 AN: 27782

GnomAD4 genome AF: 0.147 AC: 22361 AN: 152204 Hom.: 2391 Cov.: 33 AF XY: 0.142 AC XY: 10575 AN XY: 74432

African (AFR) AF: 0.309 AC: 12820 AN: 41482

American (AMR) AF: 0.0831 AC: 1271 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3472

East Asian (EAS) AF: 0.0957 AC: 496 AN: 5182

South Asian (SAS) AF: 0.0626 AC: 302 AN: 4826

European-Finnish (FIN) AF: 0.0454 AC: 482 AN: 10614

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0905 AC: 6152 AN: 68014

Other (OTH) AF: 0.123 AC: 259 AN: 2110

Alfa AF: 0.112 Hom.: 3069

Bravo AF: 0.158

Asia WGS AF: 0.136 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	12
DANN	Benign	0.59
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12855; hg19: chr1-51440093;