13-45713329-C-G

Variant names:

• chr13-45713329-C-G
• rs1950283467
• NM_152719.3:c.304C>G

Variant summary

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

The NM_152719.3(CBY2):​c.304C>G​(p.Pro102Ala) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P102S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CBY2 NM_152719.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.489
• Publications: 0 publications found

Genes affected

CBY2 (HGNC:30720): (chibby family member 2) Enables identical protein binding activity. Predicted to be located in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

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=0.052132428).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152719.3. 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
	CBY2	NM_152719.3	MANE Select	c.304C>G	p.Pro102Ala	missense	Exon 3 of 3	NP_689932.1	Q8NA61-1
	CBY2	NM_001286341.2		c.223C>G	p.Pro75Ala	missense	Exon 2 of 2	NP_001273270.1
	CBY2	NM_001286342.2		c.196C>G	p.Pro66Ala	missense	Exon 3 of 3	NP_001273271.1	Q8NA61-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBY2	ENST00000310521.6	TSL:1 MANE Select	c.304C>G	p.Pro102Ala	missense	Exon 3 of 3	ENSP00000309189.1	Q8NA61-1
	CBY2	ENST00000378966.3	TSL:1	c.196C>G	p.Pro66Ala	missense	Exon 2 of 2	ENSP00000368249.3	Q8NA61-2
	CBY2	ENST00000610924.1	TSL:5	c.196C>G	p.Pro66Ala	missense	Exon 3 of 3	ENSP00000480148.1	Q8NA61-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.8
DANN	Benign	0.82
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.49
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.031
Sift	Benign	0.14	T
Sift4G	Benign	0.15	T
Polyphen		0.0040	B
Vest4		0.090
MutPred		0.13		Gain of MoRF binding (P = 0.2756)
MVP		0.28
MPC		0.33
ClinPred		0.085	T
GERP RS		2.3
Varity_R		0.034
gMVP		0.16
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1950283467; hg19: chr13-46287464; COSMIC: COSV60117497;