rs4251698

Variant names:

• chr12-12721637-T-A
• rs4251698
• NM_004064.5:c.*610T>A

Your query was ambiguous. Multiple possible variants found:

• chr12-12721637-T-A
• chr12-12721637-T-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004064.5(CDKN1B):​c.*610T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 152,196 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (126 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDKN1B NM_004064.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.695
• Publications: 2 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• multiple endocrine neoplasia

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

  Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

ENSG00000256658 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-12721637-T-A is Benign according to our data. Variant chr12-12721637-T-A is described in ClinVar as Benign. ClinVar VariationId is 307683.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0757 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1B	NM_004064.5	MANE Select	c.*610T>A		3_prime_UTR	Exon 3 of 3	NP_004055.1	Q6I9V6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1B	ENST00000228872.9	TSL:1 MANE Select	c.*610T>A		3_prime_UTR	Exon 3 of 3	ENSP00000228872.4	P46527
	CDKN1B	ENST00000614874.2	TSL:6	c.*2691T>A		3_prime_UTR	Exon 2 of 2	ENSP00000507272.1	P46527
	CDKN1B	ENST00000907758.1		c.*581T>A		3_prime_UTR	Exon 3 of 3	ENSP00000577817.1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3671 AN: 152078 Hom.: 126 Cov.: 32

Gnomad AFR AF: 0.0776

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0201

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 600 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 364

African (AFR) AF: 0.00 AC: 0 AN: 20

American (AMR) AF: 0.00 AC: 0 AN: 12

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20

East Asian (EAS) AF: 0.00 AC: 0 AN: 18

South Asian (SAS) AF: 0.00 AC: 0 AN: 70

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 94

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 322

Other (OTH) AF: 0.00 AC: 0 AN: 42

GnomAD4 genome AF: 0.0243 AC: 3694 AN: 152196 Hom.: 126 Cov.: 32 AF XY: 0.0241 AC XY: 1793 AN XY: 74430

African (AFR) AF: 0.0779 AC: 3233 AN: 41496

American (AMR) AF: 0.0186 AC: 285 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5188

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4826

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000500 AC: 34 AN: 68006

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.0144 Hom.: 10

Bravo AF: 0.0272

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Multiple endocrine neoplasia type 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.57
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism

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: rs4251698;

hg19: chr12-12874571;