rs34330

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -16 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_StrongBP6_Strong

The NM_004064.5(CDKN1B):c.-79T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.744 (AC=1,189,757) in the gnomAD database across 1,599,978 control chromosomes, including 445,453 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.797. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38094 hom., cov: 34)

Exomes 𝑓: 0.75 ( 407359 hom. )

Consequence

CDKN1B
NM_004064.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.109

Publications

95 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
multiple endocrine neoplasia
Inheritance: AD Classification: STRONG Submitted by: G2P
hereditary nonpolyposis colon cancer
Inheritance: Unknown Classification: LIMITED Submitted by: ClinGen

CDKN1B links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004064.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -16 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BP6

ClinVar 2-star benign — strong (BP6); ClinVar germline classification: Benign/Likely Benign, 2 star(s).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.7969 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN1B	NM_004064.5	MANE Select	c.-79T>C		5_prime_UTR	Exon 1 of 3	NP_004055.1	P46527

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDKN1B	ENST00000228872.9	TSL:1 MANE Select	c.-79T>C	5_prime_UTR	Exon 1 of 3	ENSP00000228872.4	P46527
CDKN1B	ENST00000614874.2	TSL:6	c.-79T>C	5_prime_UTR	Exon 1 of 2	ENSP00000507272.1	P46527
CDKN1B	ENST00000907758.1		c.-79T>C	5_prime_UTR	Exon 1 of 3	ENSP00000577817.1	P46527

Frequencies

GnomAD3 genomes

AF:

0.701

AC:

106549

AN:

152040

Hom.:

38072

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.687

Gnomad AMR

AF:

0.763

Gnomad ASJ

AF:

0.854

Gnomad EAS

AF:

0.513

Gnomad SAS

AF:

0.782

Gnomad FIN

AF:

0.779

Gnomad MID

AF:

0.712

Gnomad NFE

AF:

0.757

Gnomad OTH

AF:

0.709

GnomAD4 exome

AF:

0.748

AC:

1083132

AN:

1447820

Hom.:

407359

Cov.:

AF XY:

0.750

AC XY:

539979

AN XY:

720408

show subpopulations

African (AFR)

AF:

0.568

AC:

18968

AN:

33366

American (AMR)

AF:

0.804

AC:

35629

AN:

44322

Ashkenazi Jewish (ASJ)

AF:

0.849

AC:

22159

AN:

26110

East Asian (EAS)

AF:

0.533

AC:

21125

AN:

39598

South Asian (SAS)

AF:

0.786

AC:

67435

AN:

85834

European-Finnish (FIN)

AF:

0.773

AC:

33699

AN:

43580

Middle Eastern (MID)

AF:

0.793

AC:

3277

AN:

4130

European-Non Finnish (NFE)

AF:

0.753

AC:

836421

AN:

1110836

Other (OTH)

AF:

0.740

AC:

44419

AN:

60044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

17113

34226

51340

68453

85566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20234

40468

60702

80936

101170

<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:

0.701

AC:

106625

AN:

152158

Hom.:

38094

Cov.:

AF XY:

0.705

AC XY:

52458

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.567

AC:

23524

AN:

41508

American (AMR)

AF:

0.764

AC:

11675

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.854

AC:

2965

AN:

3472

East Asian (EAS)

AF:

0.514

AC:

2647

AN:

5150

South Asian (SAS)

AF:

0.781

AC:

3776

AN:

4832

European-Finnish (FIN)

AF:

0.779

AC:

8253

AN:

10598

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.757

AC:

51460

AN:

67996

Other (OTH)

AF:

0.707

AC:

1494

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1642

3285

4927

6570

8212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

TOPMed (Bravo)

AF:

0.694

AC:

183746

AN:

264690

Hom.:

65016

ALFA (dbGaP/dbSNP Allele Frequency Aggregator)

AF:

0.736

AC:

349935

AN:

475342

Hom.:

130112

Local populations

ABraOM SABE-WGS-1171

AF:

0.723

AC:

1694

AN:

2342

Hom.:

618

ChinaMAP Phase 1

AF:

0.519

Denmark Genome

AF:

0.800

AC:

240

AN:

300

GenomeAsia100K

AF:

0.650

AC:

2265

AN:

3478

show subpopulations

Oceania

AF:

0.392

AC:

AN:

148

Hom.:

North-East Asia

AF:

0.598

AC:

420

AN:

702

Hom.:

122

South-East Asia

AF:

0.513

AC:

355

AN:

692

Hom.:

South Asia

AF:

0.756

AC:

1095

AN:

1448

Hom.:

419

Africa

AF:

0.582

AC:

121

AN:

208

Hom.:

America

AF:

0.885

AC:

AN:

Hom.:

West Eurasia

AF:

0.746

AC:

170

AN:

228

Hom.:

Korea4K (4,157 Koreans)

AF:

0.554

AC:

4007

AN:

7228

Qatari Genome

AF:

0.835

AC:

147

AN:

176

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.547

AC:

66980

AN:

122501

Hom.:

18241

Turkish Variome

AF:

0.778

AC:

1203

AN:

1546

Hom.:

476

UK10K

AF:

0.745

AC:

5635

AN:

7562

show subpopulations

TwinsUK

AF:

0.746

AC:

2666

AN:

3574

ALSPAC

AF:

0.745

AC:

2872

AN:

3854

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.505

AC:

4523

AN:

8960

Hom.:

1132

Case/control cohorts

Cohort

Cases

Controls

SCHEMA

(Schizophrenia)

83078 / 125160AF: 0.663774

163122 / 236512AF: 0.689699

Allele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Multiple endocrine neoplasia type 4 (5)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-0.11

PromoterAI

-0.00060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

AlphaGenome AVI

Uncertain

(source)

GPN-Star LLR

-3.3

(source)

GPN-Star score

3.3

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Pangolin (max)

Benign

0.0

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

Case/control cohorts

ClinVar

Computational scores

Splicing

Publications

Other links and lift over