NM_004196.7:c.739-1388T>G

Variant names:

• chr14-50336009-A-C
• rs7148089
• NM_004196.7:c.739-1388T>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.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 NM_004196.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 27 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL1	NM_004196.7	MANE Select	c.739-1388T>G		intron	N/A	NP_004187.3
	CDKL1	NM_001423761.1		c.739-1388T>G		intron	N/A	NP_001410690.1	Q00532-1
	CDKL1	NM_001423762.1		c.739-1388T>G		intron	N/A	NP_001410691.1	A0A9S7JKS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL1	ENST00000395834.6	TSL:1 MANE Select	c.739-1388T>G		intron	N/A	ENSP00000379176.2	A0A9S7JKS7
	CDKL1	ENST00000216378.2	TSL:1	c.742-1388T>G		intron	N/A	ENSP00000216378.2	A0A5H1ZRP5
	CDKL1	ENST00000356146.5	TSL:1	n.2966T>G		non_coding_transcript_exon	Exon 20 of 20

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

GnomAD2 exomes AF: 0.563 AC: 135635 AN: 240772 AF XY: 0.565

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 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

African (AFR) AF: 0.483 AC: 12711 AN: 26302

American (AMR) AF: 0.526 AC: 19561 AN: 37214

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 8746 AN: 16916

East Asian (EAS) AF: 0.619 AC: 10403 AN: 16808

South Asian (SAS) AF: 0.546 AC: 45400 AN: 83212

European-Finnish (FIN) AF: 0.597 AC: 18790 AN: 31448

Middle Eastern (MID) AF: 0.477 AC: 2134 AN: 4474

European-Non Finnish (NFE) AF: 0.578 AC: 551111 AN: 953822

Other (OTH) AF: 0.567 AC: 24925 AN: 43996

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

African (AFR) AF: 0.489 AC: 20251 AN: 41382

American (AMR) AF: 0.545 AC: 8308 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1817 AN: 3472

East Asian (EAS) AF: 0.624 AC: 3212 AN: 5146

South Asian (SAS) AF: 0.535 AC: 2548 AN: 4764

European-Finnish (FIN) AF: 0.595 AC: 6263 AN: 10530

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39521 AN: 67938

Other (OTH) AF: 0.556 AC: 1173 AN: 2110

Alfa AF: 0.561 Hom.: 55300

Bravo AF: 0.542

Asia WGS AF: 0.537 AC: 1866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.65
PhyloP100		0.014
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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