rs3176447

Variant names:

• chr1-50968015-T-A
• rs3176447
• NM_001429675.1:c.-1896T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-50968015-T-A
• chr1-50968015-T-C

Variant summary

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

The NM_001429675.1(CDKN2C):​c.-1896T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,354 control chromosomes in the GnomAD database, including 520 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 0.078 (520 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDKN2C NM_001429675.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• Publications: 11 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]

ENSG00000290102 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001429675.1. 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_001429675.1		c.-1896T>A		5_prime_UTR	Exon 2 of 4	NP_001416604.1	Q6ICV4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2C	ENST00000262662.5	TSL:2	c.-1896T>A		5_prime_UTR	Exon 2 of 4	ENSP00000262662.1	P42773
	CDKN2C	ENST00000855560.1		c.-1126-770T>A		intron	N/A	ENSP00000525619.1
	ENSG00000290102	ENST00000702980.2		n.598A>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11822 AN: 152234 Hom.: 518 Cov.: 33

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0620

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0604

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0867

Gnomad OTH AF: 0.0759

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0777 AC: 11834 AN: 152354 Hom.: 520 Cov.: 33 AF XY: 0.0756 AC XY: 5629 AN XY: 74504

African (AFR) AF: 0.0693 AC: 2882 AN: 41576

American (AMR) AF: 0.0619 AC: 947 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3472

East Asian (EAS) AF: 0.115 AC: 595 AN: 5186

South Asian (SAS) AF: 0.0600 AC: 290 AN: 4830

European-Finnish (FIN) AF: 0.0453 AC: 481 AN: 10628

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0867 AC: 5896 AN: 68030

Other (OTH) AF: 0.0803 AC: 170 AN: 2116

Alfa AF: 0.0323 Hom.: 21

Bravo AF: 0.0789

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.5
DANN	Benign	0.64
PhyloP100		-0.53
Mutation Taster		=300/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3176447;

hg19: chr1-51433687;