rs3783412

Positions:

• chr14-50389923-A-G

Variant summary

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

The NM_004196.7(CDKL1):​c.168+5778T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,012 control chromosomes in the GnomAD database, including 22,023 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 0.53 (22023 hom., cov: 31)
• Consequence: CDKL1 NM_004196.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

Genes affected

CDKL1 (HGNC:1781): (cyclin dependent kinase like 1) This gene product is a member of a large family of CDC2-related serine/threonine protein kinases that accumulates primarily in the nucleus. [provided by RefSeq, Nov 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKL1	NM_004196.7	c.168+5778T>C		intron_variant		ENST00000395834.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKL1	ENST00000395834.6	c.168+5778T>C		intron_variant		1	NM_004196.7	P1
CDKL1	ENST00000216378.2	c.171+5778T>C		intron_variant		1
CDKL1	ENST00000356146.5	n.970+206T>C		intron_variant, non_coding_transcript_variant		1
CDKL1	ENST00000531052.1	n.376+5778T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80123 AN: 151894 Hom.: 22000 Cov.: 31

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.494

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.528 AC: 80190 AN: 152012 Hom.: 22023 Cov.: 31 AF XY: 0.526 AC XY: 39077 AN XY: 74308

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.489

Alfa AF: 0.478 Hom.: 17396

Bravo AF: 0.537

Asia WGS AF: 0.401 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.7
DANN	Benign	0.83

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: rs3783412; hg19: chr14-50856641;