dbSNP rs735555: CDK5R1:c.*1888C>T (chr17-32490432-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003885.3(CDK5R1):c.*1888C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 167,096 control chromosomes in the GnomAD database, including 11,185 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 0.30 ( 9129 hom., cov: 33)

Exomes 𝑓: 0.52 ( 2056 hom. )

Consequence

CDK5R1
NM_003885.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.312

Publications

24 publications found

Variant links:

Genes affected

CDK5R1 (HGNC:1775): (cyclin dependent kinase 5 regulatory subunit 1) The protein encoded by this gene (p35) is a neuron-specific activator of cyclin-dependent kinase 5 (CDK5); the activation of CDK5 is required for proper development of the central nervous system. The p35 form of this protein is proteolytically cleaved by calpain, generating a p25 form. The cleavage of p35 into p25 results in relocalization of the protein from the cell periphery to nuclear and perinuclear regions. P25 deregulates CDK5 activity by prolonging its activation and changing its cellular location. The p25 form accumulates in the brain neurons of patients with Alzheimer's disease. This accumulation correlates with an increase in CDK5 kinase activity, and may lead to aberrantly phosphorylated forms of the microtubule-associated protein tau, which contributes to Alzheimer's disease. [provided by RefSeq, Jul 2008]

CDK5R1 links:

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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=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5R1	NM_003885.3 link	c.*1888C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000313401.4	NP_003876.1	Q15078Q8N619

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5R1	ENST00000313401.4 link	c.*1888C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_003885.3	ENSP00000318486.3		Q15078

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46014

AN:

152050

Hom.:

9131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0792

Gnomad AMI

AF:

0.494

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.00596

Gnomad SAS

AF:

0.236

Gnomad FIN

AF:

0.522

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.300

GnomAD4 exome

AF:

0.521

AC:

7784

AN:

14928

Hom.:

2056

Cov.:

AF XY:

0.518

AC XY:

3677

AN XY:

7092

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.523

AC:

7688

AN:

14702

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.458

AC:

AN:

120

Other (OTH)

AF:

0.413

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

207

414

622

829

1036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.302

AC:

46002

AN:

152168

Hom.:

9129

Cov.:

AF XY:

0.304

AC XY:

22629

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0789

AC:

3280

AN:

41556

American (AMR)

AF:

0.316

AC:

4841

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

1269

AN:

3470

East Asian (EAS)

AF:

0.00598

AC:

AN:

5188

South Asian (SAS)

AF:

0.238

AC:

1145

AN:

4820

European-Finnish (FIN)

AF:

0.522

AC:

5511

AN:

10560

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.423

AC:

28774

AN:

67966

Other (OTH)

AF:

0.297

AC:

626

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1467

2934

4402

5869

7336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.362

Hom.:

7135

Bravo

AF:

0.280

Asia WGS

AF:

0.108

AC:

374

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.8

(source)

DANN

Benign

0.91

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over