rs1549759

Variant names:

• chr7-151056377-A-G
• rs1549759
• NM_004935.4:c.312+203T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-151056377-A-G
• chr7-151056377-A-T

Variant summary

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

The NM_004935.4(CDK5):​c.312+203T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 603,802 control chromosomes in the GnomAD database, including 226,290 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 (58761 hom., cov: 32)
  • Exomes 𝑓: 0.86 (167529 hom.)
• Consequence: CDK5 NM_004935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK5	NM_004935.4	c.312+203T>C		intron_variant	Intron 5 of 11	ENST00000485972.6	NP_004926.1
CDK5	NM_001164410.3	c.312+203T>C		intron_variant	Intron 5 of 10		NP_001157882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK5	ENST00000485972.6	c.312+203T>C		intron_variant	Intron 5 of 11	1	NM_004935.4	ENSP00000419782.1

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133531 AN: 152110 Hom.: 58706 Cov.: 32

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.875

GnomAD4 exome AF: 0.860 AC: 388364 AN: 451574 Hom.: 167529 Cov.: 4 AF XY: 0.859 AC XY: 204465 AN XY: 238110

Gnomad4 AFR exome AF: 0.932

Gnomad4 AMR exome AF: 0.912

Gnomad4 ASJ exome AF: 0.902

Gnomad4 EAS exome AF: 0.977

Gnomad4 SAS exome AF: 0.849

Gnomad4 FIN exome AF: 0.863

Gnomad4 NFE exome AF: 0.838

Gnomad4 OTH exome AF: 0.865

GnomAD4 genome AF: 0.878 AC: 133643 AN: 152228 Hom.: 58761 Cov.: 32 AF XY: 0.878 AC XY: 65347 AN XY: 74428

Gnomad4 AFR AF: 0.929

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.908

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.864

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.877

Alfa AF: 0.867 Hom.: 17164

Bravo AF: 0.884

Asia WGS AF: 0.913 AC: 3173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.55

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: rs1549759; hg19: chr7-150753464;