Variant chr7-151055895-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004935.4(CDK5):c.313-47G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.046 in 1,325,908 control chromosomes in the GnomAD database, including 1,541 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 0.047 ( 227 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1314 hom. )

Consequence

CDK5
NM_004935.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.179

Variant links:

Genes affected

CDK5 (HGNC:1774): (cyclin dependent kinase 5) This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins. Unlike other members of the family, the protein encoded by this gene does not directly control cell cycle regulation. Instead the protein, which is predominantly expressed at high levels in mammalian postmitotic central nervous system neurons, functions in diverse processes such as synaptic plasticity and neuronal migration through phosphorylation of proteins required for cytoskeletal organization, endocytosis and exocytosis, and apoptosis. In humans, an allelic variant of the gene that results in undetectable levels of the protein has been associated with lethal autosomal recessive lissencephaly-7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

CDK5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5	NM_004935.4 linkuse as main transcript	c.313-47G>C		intron_variant		ENST00000485972.6
CDK5	NM_001164410.3 linkuse as main transcript	c.313-289G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5	ENST00000485972.6 linkuse as main transcript	c.313-47G>C	intron_variant		1	NM_004935.4	P1	Q00535-1
CDK5	ENST00000297518.4 linkuse as main transcript	c.313-289G>C	intron_variant		1			Q00535-2
CDK5	ENST00000476691.1 linkuse as main transcript	n.466G>C	non_coding_transcript_exon_variant	1/2	4
CDK5	ENST00000487703.5 linkuse as main transcript	n.677-47G>C	intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0474

AC:

7217

AN:

152184

Hom.:

229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0671

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0334

Gnomad ASJ

AF:

0.0377

Gnomad EAS

AF:

0.00981

Gnomad SAS

AF:

0.0524

Gnomad FIN

AF:

0.0298

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0445

Gnomad OTH

AF:

0.0402

GnomAD3 exomes

AF:

0.0406

AC:

7201

AN:

177296

Hom.:

180

AF XY:

0.0422

AC XY:

3985

AN XY:

94372

show subpopulations

Gnomad AFR exome

AF:

0.0685

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.0340

Gnomad EAS exome

AF:

0.00953

Gnomad SAS exome

AF:

0.0576

Gnomad FIN exome

AF:

0.0266

Gnomad NFE exome

AF:

0.0473

Gnomad OTH exome

AF:

0.0392

GnomAD4 exome

AF:

0.0458

AC:

53778

AN:

1173606

Hom.:

1314

Cov.:

AF XY:

0.0463

AC XY:

27334

AN XY:

590730

show subpopulations

Gnomad4 AFR exome

AF:

0.0694

Gnomad4 AMR exome

AF:

0.0243

Gnomad4 ASJ exome

AF:

0.0357

Gnomad4 EAS exome

AF:

0.0104

Gnomad4 SAS exome

AF:

0.0608

Gnomad4 FIN exome

AF:

0.0303

Gnomad4 NFE exome

AF:

0.0474

Gnomad4 OTH exome

AF:

0.0441

GnomAD4 genome

AF:

0.0474

AC:

7224

AN:

152302

Hom.:

227

Cov.:

AF XY:

0.0466

AC XY:

3469

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0672

Gnomad4 AMR

AF:

0.0333

Gnomad4 ASJ

AF:

0.0377

Gnomad4 EAS

AF:

0.00983

Gnomad4 SAS

AF:

0.0524

Gnomad4 FIN

AF:

0.0298

Gnomad4 NFE

AF:

0.0445

Gnomad4 OTH

AF:

0.0416

Alfa

AF:

0.0430

Hom.:

Bravo

AF:

0.0478

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over