Genetic Variant CSNK1A1:c.*1107_*1108dupTT (chr5-149495744-T-TAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001892.6(CSNK1A1):c.*1107_*1108dupTT 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 0.0053 ( 10 hom., cov: 0)

Exomes 𝑓: 0.010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CSNK1A1
NM_001892.6 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.157

Publications

0 publications found

Variant links:

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]

CSNK1A1 links:

ENSG00000230551 (HGNC:):

ENSG00000230551 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001892.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 491 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSNK1A1	NM_001892.6	MANE Select	c.1107_1108dupTT	3_prime_UTR	Exon 10 of 10	NP_001883.4
CSNK1A1	NM_001025105.3		c.1107_1108dupTT	3_prime_UTR	Exon 11 of 11	NP_001020276.1	P48729-2
CSNK1A1	NM_001271741.2		c.1107_1108dupTT	3_prime_UTR	Exon 10 of 10	NP_001258670.1	P48729-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CSNK1A1	ENST00000377843.8	TSL:1 MANE Select	c.1107_1108dupTT	3_prime_UTR	Exon 10 of 10	ENSP00000367074.2	P48729-1
CSNK1A1	ENST00000261798.10	TSL:1	c.1107_1108dupTT	3_prime_UTR	Exon 11 of 11	ENSP00000261798.6	P48729-2
ENSG00000230551	ENST00000499521.2	TSL:1	n.7204_7205dupTT	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00531

AC:

491

AN:

92528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00878

Gnomad AMI

AF:

0.00163

Gnomad AMR

AF:

0.00333

Gnomad ASJ

AF:

0.000387

Gnomad EAS

AF:

0.00279

Gnomad SAS

AF:

0.00114

Gnomad FIN

AF:

0.0204

Gnomad MID

AF:

0.00505

Gnomad NFE

AF:

0.00331

Gnomad OTH

AF:

0.00493

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0103

AC:

AN:

194

Hom.:

Cov.:

AF XY:

0.00862

AC XY:

AN XY:

116

show subpopulations

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

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0104

AC:

AN:

192

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00531

AC:

491

AN:

92508

Hom.:

Cov.:

AF XY:

0.00602

AC XY:

259

AN XY:

43022

show subpopulations

African (AFR)

AF:

0.00877

AC:

227

AN:

25894

American (AMR)

AF:

0.00333

AC:

AN:

7814

Ashkenazi Jewish (ASJ)

AF:

0.000387

AC:

AN:

2584

East Asian (EAS)

AF:

0.00280

AC:

AN:

3214

South Asian (SAS)

AF:

0.00115

AC:

AN:

2620

European-Finnish (FIN)

AF:

0.0204

AC:

AN:

3340

Middle Eastern (MID)

AF:

0.00568

AC:

AN:

176

European-Non Finnish (NFE)

AF:

0.00331

AC:

149

AN:

45034

Other (OTH)

AF:

0.00493

AC:

AN:

1218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism

(source)

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.

Publications

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5-149495744-TAAAAAAAAAAA-TAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over