Variant 1-50974240-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_078626.3(CDKN2C):c.477C>T(p.Asn159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000481 in 1,581,340 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 2 hom. )

Consequence

CDKN2C
NM_078626.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.398

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]

CDKN2C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 1-50974240-C-T is Benign according to our data. Variant chr1-50974240-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638812.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.398 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN2C	NM_078626.3 linkuse as main transcript	c.477C>T	p.Asn159=	synonymous_variant	2/2	ENST00000371761.4
CDKN2C	NM_001262.3 linkuse as main transcript	c.477C>T	p.Asn159=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDKN2C	ENST00000371761.4 linkuse as main transcript	c.477C>T	p.Asn159=	synonymous_variant	2/2	1	NM_078626.3	P1
CDKN2C	ENST00000396148.2 linkuse as main transcript	c.477C>T	p.Asn159=	synonymous_variant	3/3	1		P1
CDKN2C	ENST00000262662.5 linkuse as main transcript	c.477C>T	p.Asn159=	synonymous_variant	4/4	2		P1

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

358

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00836

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000646

AC:

147

AN:

227506

Hom.:

AF XY:

0.000418

AC XY:

AN XY:

122144

show subpopulations

Gnomad AFR exome

AF:

0.00788

Gnomad AMR exome

AF:

0.000600

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000480

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000281

AC:

402

AN:

1429108

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

160

AN XY:

706416

show subpopulations

Gnomad4 AFR exome

AF:

0.00926

Gnomad4 AMR exome

AF:

0.000525

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000491

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000384

Gnomad4 OTH exome

AF:

0.000458

GnomAD4 genome

AF:

0.00236

AC:

359

AN:

152232

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00835

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000664

Hom.:

Bravo

AF:

0.00272

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

CDKN2C: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.3

DANN

Benign

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over