rs7148089

Positions:

• chr14-50336009-A-C

Variant summary

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

The ENST00000395834.6(CDKL1):​c.739-1388T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,365,990 control chromosomes in the GnomAD database, including 222,167 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 0.55 (23229 hom., cov: 30)
  • Exomes 𝑓: 0.57 (198938 hom.)
• Consequence: CDKL1 ENST00000395834.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKL1	NM_004196.7	c.739-1388T>G		intron_variant		ENST00000395834.6	NP_004187.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKL1	ENST00000395834.6	c.739-1388T>G		intron_variant		1	NM_004196.7	ENSP00000379176	P1

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83661 AN: 151680 Hom.: 23206 Cov.: 30

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.555

GnomAD3 exomes AF: 0.563 AC: 135635 AN: 240772 Hom.: 38339 AF XY: 0.565 AC XY: 74716 AN XY: 132200

Gnomad AFR exome AF: 0.491

Gnomad AMR exome AF: 0.527

Gnomad ASJ exome AF: 0.512

Gnomad EAS exome AF: 0.619

Gnomad SAS exome AF: 0.542

Gnomad FIN exome AF: 0.596

Gnomad NFE exome AF: 0.580

Gnomad OTH exome AF: 0.559

GnomAD4 exome AF: 0.571 AC: 693781 AN: 1214192 Hom.: 198938 Cov.: 55 AF XY: 0.570 AC XY: 343252 AN XY: 601718

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.526

Gnomad4 ASJ exome AF: 0.517

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.546

Gnomad4 FIN exome AF: 0.597

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.552 AC: 83735 AN: 151798 Hom.: 23229 Cov.: 30 AF XY: 0.549 AC XY: 40749 AN XY: 74166

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.556

Alfa AF: 0.566 Hom.: 41030

Bravo AF: 0.542

Asia WGS AF: 0.537 AC: 1866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs7148089; hg19: chr14-50802727; COSMIC: COSV53579822; COSMIC: COSV53579822;