rs891507

Positions:

• chr7-151054979-T-C
• chr7-151054979-T-G

Variant summary

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

The NM_004935.4(CDK5):​c.650+48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 1,589,312 control chromosomes in the GnomAD database, including 584,574 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 0.88 (59517 hom., cov: 31)
  • Exomes 𝑓: 0.85 (525057 hom.)
• Consequence: CDK5 NM_004935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.47

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK5	NM_004935.4	c.650+48A>G		intron_variant		ENST00000485972.6
CDK5	NM_001164410.3	c.554+48A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK5	ENST00000485972.6	c.650+48A>G		intron_variant		1	NM_004935.4	P1
CDK5	ENST00000297518.4	c.554+48A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134353 AN: 152090 Hom.: 59460 Cov.: 31

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.907

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.883

GnomAD3 exomes AF: 0.876 AC: 215506 AN: 245886 Hom.: 94637 AF XY: 0.870 AC XY: 116237 AN XY: 133604

Gnomad AFR exome AF: 0.945

Gnomad AMR exome AF: 0.934

Gnomad ASJ exome AF: 0.901

Gnomad EAS exome AF: 0.958

Gnomad SAS exome AF: 0.851

Gnomad FIN exome AF: 0.866

Gnomad NFE exome AF: 0.843

Gnomad OTH exome AF: 0.874

GnomAD4 exome AF: 0.854 AC: 1227323 AN: 1437104 Hom.: 525057 Cov.: 25 AF XY: 0.853 AC XY: 611160 AN XY: 716274

Gnomad4 AFR exome AF: 0.943

Gnomad4 AMR exome AF: 0.931

Gnomad4 ASJ exome AF: 0.900

Gnomad4 EAS exome AF: 0.972

Gnomad4 SAS exome AF: 0.851

Gnomad4 FIN exome AF: 0.864

Gnomad4 NFE exome AF: 0.842

Gnomad4 OTH exome AF: 0.866

GnomAD4 genome AF: 0.883 AC: 134469 AN: 152208 Hom.: 59517 Cov.: 31 AF XY: 0.883 AC XY: 65732 AN XY: 74406

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.900

Gnomad4 ASJ AF: 0.907

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.885

Alfa AF: 0.867 Hom.: 14639

Bravo AF: 0.891

Asia WGS AF: 0.914 AC: 3178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0090
DANN	Benign	0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs891507; hg19: chr7-150752066;