rs7147228

Variant names:

• chr14-50386510-T-C
• rs7147228
• NM_004196.7:c.168+9191A>G

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+9191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 152,064 control chromosomes in the GnomAD database, including 25,938 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 0.58 (25938 hom., cov: 32)
• Consequence: CDKL1 NM_004196.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKL1	NM_004196.7	c.168+9191A>G		intron_variant	Intron 2 of 9	ENST00000395834.6	NP_004187.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKL1	ENST00000395834.6	c.168+9191A>G		intron_variant	Intron 2 of 9	1	NM_004196.7	ENSP00000379176.2
CDKL1	ENST00000216378.2	c.171+9191A>G		intron_variant	Intron 2 of 8	1		ENSP00000216378.2
CDKL1	ENST00000356146.5	n.970+3619A>G		intron_variant	Intron 7 of 19	1
CDKL1	ENST00000531052.1	n.376+9191A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87993 AN: 151946 Hom.: 25906 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.579 AC: 88082 AN: 152064 Hom.: 25938 Cov.: 32 AF XY: 0.574 AC XY: 42675 AN XY: 74310

African (AFR) AF: 0.665 AC: 27593 AN: 41474

American (AMR) AF: 0.534 AC: 8154 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1486 AN: 3468

East Asian (EAS) AF: 0.784 AC: 4062 AN: 5180

South Asian (SAS) AF: 0.566 AC: 2732 AN: 4824

European-Finnish (FIN) AF: 0.492 AC: 5184 AN: 10546

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37213 AN: 67986

Other (OTH) AF: 0.547 AC: 1157 AN: 2114

Alfa AF: 0.551 Hom.: 39781

Bravo AF: 0.586

Asia WGS AF: 0.657 AC: 2278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.80
PhyloP100		-0.24
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: rs7147228; hg19: chr14-50853228;