rs10058728

Positions:

• chr5-149524529-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000377843.8(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 ENST00000377843.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK1A1	NM_001892.6	c.357+516T>A		intron_variant		ENST00000377843.8	NP_001883.4
CSNK1A1	NM_001025105.3	c.357+516T>A		intron_variant			NP_001020276.1
CSNK1A1	NM_001271741.2	c.357+516T>A		intron_variant			NP_001258670.1
CSNK1A1	NM_001271742.2	c.90+516T>A		intron_variant			NP_001258671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK1A1	ENST00000377843.8	c.357+516T>A		intron_variant		1	NM_001892.6	ENSP00000367074	A1

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

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.642

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs10058728; hg19: chr5-148904092;