rs7330

chr12-12721983-C-Achr12-12721983-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004064.5(CDKN1B):c.*956C>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 0.562 in 152,022 control chromosomes in the GnomAD database, including 24,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (24828 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: CDKN1B NM_004064.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.795

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 12-12721983-C-A is Benign according to our data. Variant chr12-12721983-C-A is described in ClinVar as [Benign]. Clinvar id is 307688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN1B	NM_004064.5	c.*956C>A		3_prime_UTR_variant	3/3	ENST00000228872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1B	ENST00000228872.9	c.*956C>A		3_prime_UTR_variant	3/3	1	NM_004064.5	P1
CDKN1B	ENST00000614874.2	c.*3037C>A		3_prime_UTR_variant	2/2			P1
CDKN1B	ENST00000682620.1	n.2708C>A		non_coding_transcript_exon_variant	4/4
CDKN1B	ENST00000684771.1	n.1662C>A		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85410 AN: 151904 Hom.: 24837 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.562 AC: 85409 AN: 152022 Hom.: 24828 Cov.: 33 AF XY: 0.565 AC XY: 41968 AN XY: 74304

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.718

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.574

Alfa AF: 0.601 Hom.: 26369

Bravo AF: 0.549

Asia WGS AF: 0.729 AC: 2531 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Multiple endocrine neoplasia type 4 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	11
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs7330; hg19: chr12-12874917;