22-38668022-G-A

Position:

• chr22-38668022-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015373.4(CBY1):​c.-33G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBY1 NM_015373.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

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]

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

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15999621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBY1	NM_015373.4	c.-33G>A		5_prime_UTR_variant	2/5	ENST00000216029.8	NP_056188.1
CBY1	NM_001002880.4	c.-33G>A		5_prime_UTR_variant	3/6		NP_001002880.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBY1	ENST00000216029.8	c.-33G>A		5_prime_UTR_variant	2/5	1	NM_015373.4	ENSP00000216029	P1
TOMM22-DT	ENST00000431924.3	n.439C>T		non_coding_transcript_exon_variant	2/2	3
	ENST00000423346.1	n.181+548C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.97G>A (p.E33K) alteration is located in exon 4 (coding exon 2) of the CBY1 gene. This alteration results from a G to A substitution at nucleotide position 97, causing the glutamic acid (E) at amino acid position 33 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.7
DANN	Benign	0.90
DEOGEN2	Benign	0.086	T
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.16	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.28	T
Sift4G	Pathogenic	0.0	D
Vest4		0.18
MVP		0.71
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.025

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-39064027;