Variant 22-38668111-A-ATC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5

The NM_015373.4(CBY1):c.64_65dup(p.Asn23ProfsTer24) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,459,260 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CBY1
NM_015373.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.68

Variant links:

Genes affected

CBY1 (HGNC:1307): (chibby 1, beta catenin antagonist) Beta-catenin is a transcriptional activator and oncoprotein involved in the development of several cancers. The protein encoded by this gene interacts directly with the C-terminal region of beta-catenin, inhibiting oncogenic beta-catenin-mediated transcriptional activation by competing with transcription factors for binding to beta-catenin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CBY1 links:

TOMM22-DT (HGNC:56758): (TOMM22 divergent transcript)

TOMM22-DT links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.85 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 22-38668111-A-ATC is Pathogenic according to our data. Variant chr22-38668111-A-ATC is described in ClinVar as [Pathogenic]. Clinvar id is 694265.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBY1	NM_015373.4 linkuse as main transcript	c.64_65dup	p.Asn23ProfsTer24	frameshift_variant	2/5	ENST00000216029.8	NP_056188.1
CBY1	NM_001002880.4 linkuse as main transcript	c.64_65dup	p.Asn23ProfsTer24	frameshift_variant	3/6		NP_001002880.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CBY1	ENST00000216029.8 linkuse as main transcript	c.64_65dup	p.Asn23ProfsTer24	frameshift_variant	2/5	1	NM_015373.4	ENSP00000216029	P1
TOMM22-DT	ENST00000431924.3 linkuse as main transcript	n.349_350insGA		non_coding_transcript_exon_variant	2/2	3
	ENST00000423346.1 linkuse as main transcript	n.181+458_181+459insGA		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251462

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459260

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Familial aplasia of the vermis

Pathogenic:1

Pathogenic, no assertion criteria provided

research

Department of Medical Genetics, Oslo University Hospital

Jan 01, 2018

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over