rs6494466

Variant names:

• chr15-64216564-G-A
• rs6494466
• NM_022048.5:c.442C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-64216564-G-A
• chr15-64216564-G-C
• chr15-64216564-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022048.5(CSNK1G1):​c.442C>T​(p.Leu148Leu) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.315 in 1,612,682 control chromosomes in the GnomAD database, including 100,590 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.44 (20290 hom., cov: 31)
  • Exomes 𝑓: 0.30 (80300 hom.)
• Consequence: CSNK1G1 NM_022048.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.001131
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98
• Publications: 37 publications found

Genes affected

CSNK1G1 (HGNC:2454): (casein kinase 1 gamma 1) This gene encodes a member of the casein kinase I gene family. This family is comprised of serine/threonine kinases that phosphorylate acidic proteins such as caseins. The encoded kinase plays a role in cell cycle checkpoint arrest in response to stalled replication forks by phosphorylating Claspin. A mutation in this gene may be associated with non-syndromic early-onset epilepsy (NSEOE). [provided by RefSeq, Jul 2016]

CSNK1G1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000259316 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022048.5. 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
	CSNK1G1	NM_022048.5	MANE Select	c.442C>T	p.Leu148Leu	splice_region synonymous	Exon 5 of 12	NP_071331.2	Q9HCP0-1
	CSNK1G1	NM_001329605.2		c.442C>T	p.Leu148Leu	splice_region synonymous	Exon 5 of 13	NP_001316534.1	U3KQB3
	CSNK1G1	NM_001329607.2		c.442C>T	p.Leu148Leu	splice_region synonymous	Exon 5 of 12	NP_001316536.1	Q8IXA3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1G1	ENST00000303052.13	TSL:1 MANE Select	c.442C>T	p.Leu148Leu	splice_region synonymous	Exon 5 of 12	ENSP00000305777.7	Q9HCP0-1
	CSNK1G1	ENST00000607537.6	TSL:1	c.442C>T	p.Leu148Leu	splice_region synonymous	Exon 5 of 13	ENSP00000475724.1	U3KQB3
	CSNK1G1	ENST00000561349.6	TSL:1	c.442C>T	p.Leu148Leu	splice_region synonymous	Exon 4 of 11	ENSP00000476088.2	Q8IXA3

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66878 AN: 151898 Hom.: 20238 Cov.: 31

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.407

GnomAD2 exomes AF: 0.344 AC: 86006 AN: 249966 AF XY: 0.355

Gnomad AFR exome AF: 0.871

Gnomad AMR exome AF: 0.234

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.125

Gnomad FIN exome AF: 0.229

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.302 AC: 441348 AN: 1460666 Hom.: 80300 Cov.: 33 AF XY: 0.312 AC XY: 226938 AN XY: 726680

African (AFR) AF: 0.886 AC: 29655 AN: 33458

American (AMR) AF: 0.239 AC: 10665 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 10465 AN: 26116

East Asian (EAS) AF: 0.145 AC: 5741 AN: 39696

South Asian (SAS) AF: 0.649 AC: 55988 AN: 86210

European-Finnish (FIN) AF: 0.234 AC: 12450 AN: 53308

Middle Eastern (MID) AF: 0.477 AC: 2746 AN: 5762

European-Non Finnish (NFE) AF: 0.264 AC: 293219 AN: 1111078

Other (OTH) AF: 0.338 AC: 20419 AN: 60338

GnomAD4 genome AF: 0.441 AC: 66971 AN: 152016 Hom.: 20290 Cov.: 31 AF XY: 0.437 AC XY: 32509 AN XY: 74314

African (AFR) AF: 0.857 AC: 35565 AN: 41482

American (AMR) AF: 0.283 AC: 4314 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1425 AN: 3468

East Asian (EAS) AF: 0.133 AC: 686 AN: 5170

South Asian (SAS) AF: 0.638 AC: 3070 AN: 4814

European-Finnish (FIN) AF: 0.231 AC: 2444 AN: 10558

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18191 AN: 67942

Other (OTH) AF: 0.402 AC: 850 AN: 2112

Alfa AF: 0.320 Hom.: 41114

Bravo AF: 0.457

Asia WGS AF: 0.398 AC: 1384 AN: 3478

EpiCase AF: 0.287

EpiControl AF: 0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		4.0
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0011
dbscSNV1_RF	Benign	0.048
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: rs6494466; hg19: chr15-64508763; COSMIC: COSV57311782; COSMIC: COSV57311782;