chr1-50971575-A-G

Position:

• chr1-50971575-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908

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

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	Protein	UniProt
CDKN2C	NM_078626.3	c.129+1078A>G		intron_variant		ENST00000371761.4	NP_523240.1
CDKN2C	NM_001262.3	c.129+1078A>G		intron_variant			NP_001253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2C	ENST00000371761.4	c.129+1078A>G		intron_variant		1	NM_078626.3	ENSP00000360826	P1
CDKN2C	ENST00000396148.2	c.129+1078A>G		intron_variant		1		ENSP00000379452	P1
CDKN2C	ENST00000262662.5	c.129+1078A>G		intron_variant		2		ENSP00000262662	P1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46695 AN: 152010 Hom.: 7483 Cov.: 33

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

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

Other links and lift over

dbSNP: rs3176459; hg19: chr1-51437247;