chr5-149524529-A-T

Variant names:

• chr5-149524529-A-T
• rs10058728
• NM_001892.6:c.357+516T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001892.6(CSNK1A1):​c.357+516T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,940 control chromosomes in the GnomAD database, including 32,976 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 0.65 (32976 hom., cov: 31)
• Consequence: CSNK1A1 NM_001892.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 25 publications found

Genes affected

CSNK1A1 (HGNC:2451): (casein kinase 1 alpha 1) Enables protein serine/threonine kinase activity. Involved in several processes, including negative regulation of canonical Wnt signaling pathway; peptidyl-serine phosphorylation; and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in centrosome; cytosol; and nuclear speck. Part of beta-catenin destruction complex. Colocalizes with keratin filament and mRNA cleavage and polyadenylation specificity factor complex. Biomarker of Alzheimer's disease and inclusion body myositis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001892.6. 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
	CSNK1A1	NM_001892.6	MANE Select	c.357+516T>A		intron	N/A	NP_001883.4
	CSNK1A1	NM_001025105.3		c.357+516T>A		intron	N/A	NP_001020276.1
	CSNK1A1	NM_001271741.2		c.357+516T>A		intron	N/A	NP_001258670.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1A1	ENST00000377843.8	TSL:1 MANE Select	c.357+516T>A		intron	N/A	ENSP00000367074.2
	CSNK1A1	ENST00000261798.10	TSL:1	c.357+516T>A		intron	N/A	ENSP00000261798.6
	CSNK1A1	ENST00000606719.6	TSL:2	c.357+516T>A		intron	N/A	ENSP00000475319.2

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97975 AN: 151822 Hom.: 32908 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.646 AC: 98107 AN: 151940 Hom.: 32976 Cov.: 31 AF XY: 0.648 AC XY: 48132 AN XY: 74258

African (AFR) AF: 0.791 AC: 32809 AN: 41486

American (AMR) AF: 0.693 AC: 10582 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1855 AN: 3466

East Asian (EAS) AF: 0.995 AC: 5156 AN: 5182

South Asian (SAS) AF: 0.697 AC: 3352 AN: 4806

European-Finnish (FIN) AF: 0.529 AC: 5580 AN: 10540

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.541 AC: 36758 AN: 67886

Other (OTH) AF: 0.642 AC: 1354 AN: 2108

Alfa AF: 0.576 Hom.: 14462

Bravo AF: 0.667

Asia WGS AF: 0.854 AC: 2957 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.78
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: rs10058728; hg19: chr5-148904092;