chr17-32490432-C-T

Position:

• chr17-32490432-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CDK5R1	NM_003885.3	c.*1888C>T		3_prime_UTR_variant	2/2	ENST00000313401.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5R1	ENST00000313401.4	c.*1888C>T		3_prime_UTR_variant	2/2	1	NM_003885.3	P1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46014 AN: 152050 Hom.: 9131 Cov.: 33

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.: 0 AF XY: 0.518 AC XY: 3677 AN XY: 7092

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.523

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.413

GnomAD4 genome AF: 0.302 AC: 46002 AN: 152168 Hom.: 9129 Cov.: 33 AF XY: 0.304 AC XY: 22629 AN XY: 74380

Gnomad4 AFR AF: 0.0789

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.00598

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.297

Alfa AF: 0.357 Hom.: 3887

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
DANN	Benign	0.91

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

Other links and lift over

dbSNP: rs735555; hg19: chr17-30817450; COSMIC: COSV57830827; COSMIC: COSV57830827;