rs549943001

Variant names:

• chr12-12717714-C-G
• rs549943001
• NM_004064.5:c.-126C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-12717714-C-G
• chr12-12717714-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004064.5(CDKN1B):​c.-126C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,636 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CDKN1B NM_004064.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen
• multiple endocrine neoplasia

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

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1B	NM_004064.5	c.-126C>G		5_prime_UTR_variant	Exon 1 of 3	ENST00000228872.9	NP_004055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1B	ENST00000228872.9	c.-126C>G		5_prime_UTR_variant	Exon 1 of 3	1	NM_004064.5	ENSP00000228872.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406636 Hom.: 0 Cov.: 35 AF XY: 0.00000143 AC XY: 1 AN XY: 697454

African (AFR) AF: 0.00 AC: 0 AN: 32116

American (AMR) AF: 0.00 AC: 0 AN: 37404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25580

East Asian (EAS) AF: 0.00 AC: 0 AN: 36850

South Asian (SAS) AF: 0.00 AC: 0 AN: 82182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4090

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094086

Other (OTH) AF: 0.0000170 AC: 1 AN: 58714

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.62
PhyloP100		1.1
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Other links and lift over

dbSNP: rs549943001; hg19: chr12-12870648;