Variant 17-32488049-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_003885.3(CDK5R1):c.429C>T(p.Ile143=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000326 in 1,612,438 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 3 hom. )

Consequence

CDK5R1
NM_003885.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.206

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 17-32488049-C-T is Benign according to our data. Variant chr17-32488049-C-T is described in ClinVar as [Benign]. Clinvar id is 728177.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.206 with no splicing effect.

BS2

High AC in GnomAd at 280 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5R1	NM_003885.3 linkuse as main transcript	c.429C>T	p.Ile143=	synonymous_variant	2/2	ENST00000313401.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CDK5R1	ENST00000313401.4 linkuse as main transcript	c.429C>T	p.Ile143=	synonymous_variant	2/2	1	NM_003885.3	P1
CDK5R1	ENST00000584716.1 linkuse as main transcript	c.255C>T	p.Ile85=	synonymous_variant, NMD_transcript_variant	1/3	1
CDK5R1	ENST00000584792.5 linkuse as main transcript	c.255C>T	p.Ile85=	synonymous_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

280

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00646

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000468

AC:

117

AN:

250194

Hom.:

AF XY:

0.000303

AC XY:

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.00705

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000168

AC:

245

AN:

1460104

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

726208

show subpopulations

Gnomad4 AFR exome

AF:

0.00631

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.00184

AC:

280

AN:

152334

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

129

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00645

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00155

Hom.:

Bravo

AF:

0.00234

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.95

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over