chr14-50389923-A-G

Variant names:

• chr14-50389923-A-G
• rs3783412
• NM_004196.7:c.168+5778T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004196.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL1	NM_004196.7	MANE Select	c.168+5778T>C		intron	N/A	NP_004187.3
	CDKL1	NM_001423761.1		c.168+5778T>C		intron	N/A	NP_001410690.1
	CDKL1	NM_001423762.1		c.168+5778T>C		intron	N/A	NP_001410691.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL1	ENST00000395834.6	TSL:1 MANE Select	c.168+5778T>C		intron	N/A	ENSP00000379176.2
	CDKL1	ENST00000216378.2	TSL:1	c.171+5778T>C		intron	N/A	ENSP00000216378.2
	CDKL1	ENST00000356146.5	TSL:1	n.970+206T>C		intron	N/A

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

African (AFR) AF: 0.677 AC: 28052 AN: 41454

American (AMR) AF: 0.497 AC: 7591 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1621 AN: 3468

East Asian (EAS) AF: 0.479 AC: 2474 AN: 5168

South Asian (SAS) AF: 0.295 AC: 1421 AN: 4822

European-Finnish (FIN) AF: 0.500 AC: 5277 AN: 10562

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31962 AN: 67948

Other (OTH) AF: 0.489 AC: 1032 AN: 2112

Alfa AF: 0.486 Hom.: 23632

Bravo AF: 0.537

Asia WGS AF: 0.401 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.7
DANN	Benign	0.83
PhyloP100		0.097
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3783412; hg19: chr14-50856641;