chr12-12717761-T-C

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_004064.5(CDKN1B):c.-79T>C 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 allele was found at a cumulative frequency of 0.744 (AC=1,189,757) in the gnomAD database across 1,599,978 control chromosomes, including 445,453 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.797. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.70 (38094 hom., cov: 34)
  • Exomes 𝑓: 0.75 (407359 hom.)
• Consequence: CDKN1B NM_004064.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.109
• Publications: 96 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: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.797 — exceeds 1% threshold (B1 applied)

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>C	5_prime_UTR	Exon 1 of 3	Prot: NP_004055.1 UniProt:

CDKN1B NM_004064.5

MANE Select

HGVSc / HGVSpc.-79T>C

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>C	5_prime_UTR	Exon 1 of 3	Prot: ENSP00000228872.4 UniProt:
	CDKN1B ENST00000614874.2	TSL:6	c.-79T>C	5_prime_UTR	Exon 1 of 2	Prot: ENSP00000507272.1 UniProt:
	CDKN1B ENST00000907758.1		c.-79T>C	5_prime_UTR	Exon 1 of 3	Prot: ENSP00000577817.1 UniProt:

CDKN1B ENST00000228872.9

TSL:1MANE Select

HGVSc / HGVSpc.-79T>C

Exon rankExon 1 of 3

5_prime_UTR

Prot: ENSP00000228872.4UniProt: P46527

CDKN1B ENST00000614874.2

TSL:6

HGVSc / HGVSpc.-79T>C

Exon rankExon 1 of 2

5_prime_UTR

Prot: ENSP00000507272.1UniProt: P46527

CDKN1B ENST00000907758.1

HGVSc / HGVSpc.-79T>C

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 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.701	AC:106549	Hom:38072	AN:152040	Cov:34
GnomAD4 exome	AF: 0.748	AC:1083132	Hom:407359	AN:1447820	Cov:73
GnomAD4 genome	AF: 0.701	AC:106625	Hom:38094	AN:152158	Cov:34
TOPMed (Bravo)	AF: 0.694	AC:183746	Hom:65016	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.736	AC:349935	Hom:130112	AN:475342	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.723	AC:1694	Hom:618	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.519	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.800	AC:240	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.650	AC:2265	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.554	AC:4007	Hom:	AN:7228	Cov:
Qatari Genome	AF: 0.835	AC:147	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.547	AC:66980	Hom:18241	AN:122501	Cov:
Turkish Variome	AF: 0.778	AC:1203	Hom:476	AN:1546	Cov:
UK10K	AF: 0.745	AC:5635	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.505	AC:4523	Hom:1132	AN:8960	Cov:

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.664	83078	125160	0.690	163122	236512

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Multiple endocrine neoplasia type 4 (5)
-	-	2	not provided (2)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	11
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.92
GPN-Star LLR	N/A	-3.3
GPN-Star score	N/A	3.3
Mutation Taster	N/A	300/0	polymorphism (auto)
PhyloP100	Benign	-0.11
PromoterAI	N/A	-0.00060	Neutral
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.0

Showing 11 of 11 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;

COSMIC: COSV57430533;

COSMIC: COSV57430533;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar