dbSNP rs3093736: CDKN1B:c.*9-669G>A (chr12-12720367-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_004064.5(CDKN1B):c.*9-669G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 152,236 control chromosomes in the GnomAD database, including 59 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 0.023 ( 59 hom., cov: 32)

Consequence

CDKN1B
NM_004064.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.130

Publications

11 publications found

Variant links:

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

CDKN1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0228 (3466/152236) while in subpopulation NFE AF = 0.0319 (2170/68006). AF 95% confidence interval is 0.0308. There are 59 homozygotes in GnomAd4. There are 1729 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 59 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1B	NM_004064.5 link	c.*9-669G>A		intron_variant	Intron 2 of 2	ENST00000228872.9	NP_004055.1	P46527Q6I9V6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1B	ENST00000228872.9 link	c.*9-669G>A		intron_variant	Intron 2 of 2	1	NM_004064.5	ENSP00000228872.4		P46527

Frequencies

GnomAD3 genomes

AF:

0.0228

AC:

3466

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00521

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00943

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00765

Gnomad FIN

AF:

0.0700

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0319

Gnomad OTH

AF:

0.0168

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

GnomAD4 genome

AF:

0.0228

AC:

3466

AN:

152236

Hom.:

Cov.:

AF XY:

0.0232

AC XY:

1729

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00520

AC:

216

AN:

41548

American (AMR)

AF:

0.00942

AC:

144

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

101

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00786

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0700

AC:

740

AN:

10578

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0319

AC:

2170

AN:

68006

Other (OTH)

AF:

0.0166

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

176

351

527

702

878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0291

Hom.:

Bravo

AF:

0.0179

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.0

(source)

DANN

Benign

0.28

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over