14-50342977-G-A

Position:

• chr14-50342977-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004196.7(CDKL1):​c.364-755C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,356,348 control chromosomes in the GnomAD database, including 30 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 0.0069 (21 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (9 hom.)
• Consequence: CDKL1 NM_004196.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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]

CDKL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00693 (1054/152144) while in subpopulation AFR AF= 0.0242 (1005/41480). AF 95% confidence interval is 0.023. There are 21 homozygotes in gnomad4. There are 500 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKL1	NM_004196.7	c.364-755C>T		intron_variant		ENST00000395834.6	NP_004187.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKL1	ENST00000395834.6	c.364-755C>T		intron_variant		1	NM_004196.7	ENSP00000379176.2
CDKL1	ENST00000216378.2	c.367-755C>T		intron_variant		1		ENSP00000216378.2
CDKL1	ENST00000356146.5	n.2308C>T		non_coding_transcript_exon_variant	16/20	1
CDKL1	ENST00000528197.5	n.422-755C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.00693 AC: 1053 AN: 152026 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.00150 AC: 335 AN: 223716 Hom.: 7 AF XY: 0.00126 AC XY: 154 AN XY: 122578

Gnomad AFR exome AF: 0.0225

Gnomad AMR exome AF: 0.000646

Gnomad ASJ exome AF: 0.000106

Gnomad EAS exome AF: 0.000180

Gnomad SAS exome AF: 0.0000358

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000275

Gnomad OTH exome AF: 0.000531

GnomAD4 exome AF: 0.000908 AC: 1094 AN: 1204204 Hom.: 9 Cov.: 30 AF XY: 0.000792 AC XY: 472 AN XY: 595706

Gnomad4 AFR exome AF: 0.0255

Gnomad4 AMR exome AF: 0.000668

Gnomad4 ASJ exome AF: 0.0000603

Gnomad4 EAS exome AF: 0.000123

Gnomad4 SAS exome AF: 0.0000616

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000354

Gnomad4 OTH exome AF: 0.00144

GnomAD4 genome AF: 0.00693 AC: 1054 AN: 152144 Hom.: 21 Cov.: 32 AF XY: 0.00672 AC XY: 500 AN XY: 74364

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00394 Hom.: 1

Bravo AF: 0.00782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.26
DANN	Benign	0.74

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: rs11570829; hg19: chr14-50809695;