dbSNP rs3759216: CDKN1B:n.2305G>A (chr12-12715152-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000682080.1(CDKN1B):n.2305G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,116 control chromosomes in the GnomAD database, including 12,103 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 0.39 ( 12103 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

CDKN1B
ENST00000682080.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.840

Publications

22 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 links:

GPR19 (HGNC:4473): (G protein-coupled receptor 19) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cilium. [provided by Alliance of Genome Resources, Apr 2022]

GPR19 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=-0.68).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR19	XM_011520623.4 link	c.-205+559C>T		intron_variant	Intron 1 of 3		XP_011518925.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CDKN1B	ENST00000682080.1 link	n.2305G>A	non_coding_transcript_exon_variant	Exon 3 of 3
CDKN1B	ENST00000477087.1 link	n.47+48G>A	intron_variant	Intron 1 of 3	3
CDKN1B	ENST00000682620.1 link	n.1631-3673G>A	intron_variant	Intron 2 of 3
CDKN1B	ENST00000684771.1 link	n.585-3673G>A	intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58777

AN:

151992

Hom.:

12104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.472

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.377

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.386

AC:

58783

AN:

152110

Hom.:

12103

Cov.:

AF XY:

0.390

AC XY:

29025

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.235

AC:

9740

AN:

41482

American (AMR)

AF:

0.381

AC:

5824

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

1636

AN:

3466

East Asian (EAS)

AF:

0.438

AC:

2267

AN:

5176

South Asian (SAS)

AF:

0.449

AC:

2166

AN:

4826

European-Finnish (FIN)

AF:

0.505

AC:

5334

AN:

10570

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.450

AC:

30598

AN:

67990

Other (OTH)

AF:

0.375

AC:

792

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1823

3647

5470

7294

9117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.423

Hom.:

13020

Bravo

AF:

0.373

Asia WGS

AF:

0.403

AC:

1400

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.84

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over