5-149495744-TAAAAAAAAAAA-TAAAAAAAAAA

Variant names:

• chr5-149495744-TA-T
• rs149346325
• NM_001892.6:c.*1108delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001892.6(CSNK1A1):​c.*1108delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.017 (21 hom., cov: 0)
  • Exomes 𝑓: 0.068 (0 hom.)
• Consequence: CSNK1A1 NM_001892.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 0 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]

ENSG00000230551 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0166 (1541/92564) while in subpopulation AFR AF = 0.0391 (1012/25904). AF 95% confidence interval is 0.0371. There are 21 homozygotes in GnomAd4. There are 766 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1541 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1A1	NM_001892.6	MANE Select	c.*1108delT		3_prime_UTR	Exon 10 of 10	NP_001883.4
	CSNK1A1	NM_001025105.3		c.*1108delT		3_prime_UTR	Exon 11 of 11	NP_001020276.1	P48729-2
	CSNK1A1	NM_001271741.2		c.*1108delT		3_prime_UTR	Exon 10 of 10	NP_001258670.1	P48729-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1A1	ENST00000377843.8	TSL:1 MANE Select	c.*1108delT		3_prime_UTR	Exon 10 of 10	ENSP00000367074.2	P48729-1
	CSNK1A1	ENST00000261798.10	TSL:1	c.*1108delT		3_prime_UTR	Exon 11 of 11	ENSP00000261798.6	P48729-2
	ENSG00000230551	ENST00000499521.2	TSL:1	n.7205delT		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 1540 AN: 92584 Hom.: 21 Cov.: 0

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.00434

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.00240

Gnomad MID AF: 0.0404

Gnomad NFE AF: 0.00386

Gnomad OTH AF: 0.0156

GnomAD4 exome AF: 0.0677 AC: 13 AN: 192 Hom.: 0 Cov.: 0 AF XY: 0.0862 AC XY: 10 AN XY: 116

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0684 AC: 13 AN: 190

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000139499), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0166 AC: 1541 AN: 92564 Hom.: 21 Cov.: 0 AF XY: 0.0178 AC XY: 766 AN XY: 43036

African (AFR) AF: 0.0391 AC: 1012 AN: 25904

American (AMR) AF: 0.0224 AC: 175 AN: 7814

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 61 AN: 2586

East Asian (EAS) AF: 0.00435 AC: 14 AN: 3216

South Asian (SAS) AF: 0.0267 AC: 70 AN: 2622

European-Finnish (FIN) AF: 0.00240 AC: 8 AN: 3340

Middle Eastern (MID) AF: 0.0455 AC: 8 AN: 176

European-Non Finnish (NFE) AF: 0.00386 AC: 174 AN: 45074

Other (OTH) AF: 0.0156 AC: 19 AN: 1218

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs149346325;

hg19: chr5-148875307;