chr12-12717761-T-G

Variant names:

• chr12-12717761-T-G
• rs34330
• NM_004064.5:c.-79T>G

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_004064.5(CDKN1B):c.-79T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The gene CDKN1B is a tumor suppressor gene (CancerMine: 40 TSG, 25 oncogene, 5 driver citations). The gene CDKN1B is a known oncogene (CancerMine: 40 TSG, 25 oncogene, 5 driver citations). The gene CDKN1B is a cancer driver gene (CancerMine: 40 TSG, 25 oncogene, 5 driver citations). The variant has a gnomAD grpmax filtering allele frequency (95% CI) of 0.0000009, indicating it is observed in the general population. Note: a gnomAD entry for this variant shows a statistical allele-bias signature, consistent with mosaic/somatic contamination (e.g. age-related clonal hematopoiesis) rather than true inherited population frequency — this frequency should not be read as evidence of a common, benign germline variant. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDKN1B NM_004064.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 18 publications found

Genes affected

CDKN1B (HGNC:1785): (cyclin dependent kinase inhibitor 1B) This gene encodes a cyclin-dependent kinase inhibitor, which shares a limited similarity with CDK inhibitor CDKN1A/p21. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes, and thus controls the cell cycle progression at G1. The degradation of this protein, which is triggered by its CDK dependent phosphorylation and subsequent ubiquitination by SCF complexes, is required for the cellular transition from quiescence to the proliferative state. Mutations in this gene are associated with multiple endocrine neoplasia type IV (MEN4). [provided by RefSeq, Apr 2014]

CDKN1B Gene-Disease associations (from GenCC):

• multiple endocrine neoplasia type 4

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
• multiple endocrine neoplasia

  Inheritance: AD Classification: STRONG Submitted by: G2P
• hereditary nonpolyposis colon cancer

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = 0.000001, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_004064.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CDKN1B NM_004064.5	MANE Select	c.-79T>G	5_prime_UTR	Exon 1 of 3	Prot: NP_004055.1 UniProt:

CDKN1B NM_004064.5

MANE Select

HGVSc / HGVSpc.-79T>G

Exon rankExon 1 of 3

5_prime_UTR

Prot: NP_004055.1UniProt: P46527Q6I9V6

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CDKN1B ENST00000228872.9	TSL:1MANE Select	c.-79T>G	5_prime_UTR	Exon 1 of 3	Prot: ENSP00000228872.4 UniProt:
	CDKN1B ENST00000614874.2	TSL:6	c.-79T>G	5_prime_UTR	Exon 1 of 2	Prot: ENSP00000507272.1 UniProt:
	CDKN1B ENST00000907758.1		c.-79T>G	5_prime_UTR	Exon 1 of 3	Prot: ENSP00000577817.1 UniProt:

CDKN1B ENST00000228872.9

TSL:1MANE Select

HGVSc / HGVSpc.-79T>G

Exon rankExon 1 of 3

5_prime_UTR

Prot: ENSP00000228872.4UniProt: P46527

CDKN1B ENST00000614874.2

TSL:6

HGVSc / HGVSpc.-79T>G

Exon rankExon 1 of 2

5_prime_UTR

Prot: ENSP00000507272.1UniProt: P46527

CDKN1B ENST00000907758.1

HGVSc / HGVSpc.-79T>G

Exon rankExon 1 of 3

5_prime_UTR

Prot: ENSP00000577817.1UniProt: P46527

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:34
GnomAD4 exome Warning	AF: 6.91e-7	AC:1	Hom:0	AN:1447946	Cov:73
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:34

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	11
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.93
GPN-Star LLR	N/A	-4.0
GPN-Star score	N/A	4.0
PhyloP100	Benign	-0.11
PromoterAI	N/A	0.0026	Neutral

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs34330;

hg19: chr12-12870695;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar