rs193920893

Variant names:

• chr22-38673201-C-G
• rs193920893
• NM_015373.4:c.346C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-38673201-C-G
• chr22-38673201-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015373.4(CBY1):​c.346C>G​(p.Leu116Val) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CBY1 NM_015373.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.510
• Publications: 1 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05188057).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015373.4. 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
	CBY1	NM_015373.4	MANE Select	c.346C>G	p.Leu116Val	missense	Exon 5 of 5	NP_056188.1	Q9Y3M2
	CBY1	NM_001002880.4		c.346C>G	p.Leu116Val	missense	Exon 6 of 6	NP_001002880.3	Q9Y3M2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBY1	ENST00000216029.8	TSL:1 MANE Select	c.346C>G	p.Leu116Val	missense	Exon 5 of 5	ENSP00000216029.3	Q9Y3M2
	TOMM22-DT	ENST00000444381.1	TSL:1	n.96-1504G>C		intron	N/A
	CBY1	ENST00000930725.1		c.355C>G	p.Leu119Val	missense	Exon 6 of 6	ENSP00000600784.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	2.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.51
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.034
Sift	Benign	0.28	T
Sift4G	Benign	0.17	T
Polyphen		0.10	B
Vest4		0.091
MutPred		0.15		Loss of helix (P = 0.0626)
MVP		0.28
MPC		0.27
ClinPred		0.12	T
GERP RS		-1.9
Varity_R		0.037
gMVP		0.19
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs193920893; hg19: chr22-39069206; COSMIC: COSV53264516; COSMIC: COSV53264516;