12-12720299-G-C

Variant names:

• chr12-12720299-G-C
• rs34329
• NM_004064.5:c.*9-737G>C

Variant summary

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

The NM_004064.5(CDKN1B):​c.*9-737G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 151,948 control chromosomes in the GnomAD database, including 29,868 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 0.61 (29868 hom., cov: 32)
• Consequence: CDKN1B NM_004064.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1B	NM_004064.5	MANE Select	c.*9-737G>C		intron	N/A	NP_004055.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1B	ENST00000228872.9	TSL:1 MANE Select	c.*9-737G>C		intron	N/A	ENSP00000228872.4
	CDKN1B	ENST00000614874.2	TSL:6	c.*1353G>C		3_prime_UTR	Exon 2 of 2	ENSP00000507272.1
	CDKN1B	ENST00000396340.1	TSL:3	c.476-766G>C		intron	N/A	ENSP00000379629.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93360 AN: 151830 Hom.: 29880 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.873

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.614 AC: 93358 AN: 151948 Hom.: 29868 Cov.: 32 AF XY: 0.613 AC XY: 45520 AN XY: 74250

African (AFR) AF: 0.445 AC: 18421 AN: 41416

American (AMR) AF: 0.551 AC: 8396 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2404 AN: 3470

East Asian (EAS) AF: 0.872 AC: 4521 AN: 5182

South Asian (SAS) AF: 0.746 AC: 3595 AN: 4816

European-Finnish (FIN) AF: 0.681 AC: 7181 AN: 10540

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46891 AN: 67968

Other (OTH) AF: 0.618 AC: 1305 AN: 2112

Alfa AF: 0.655 Hom.: 4109

Bravo AF: 0.599

Asia WGS AF: 0.744 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		-0.98
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs34329; hg19: chr12-12873233;