chr22-38657377-A-G

Variant names:

• chr22-38657377-A-G
• rs2064088
• NM_015373.4:c.-39+627A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015373.4(CBY1):​c.-39+627A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,048 control chromosomes in the GnomAD database, including 6,643 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6643 hom., cov: 32)
• Consequence: CBY1 NM_015373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 6 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]

CBY1 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBY1	NM_015373.4	c.-39+627A>G		intron_variant	Intron 1 of 4	ENST00000216029.8	NP_056188.1
CBY1	NM_001002880.4	c.-179+627A>G		intron_variant	Intron 1 of 5		NP_001002880.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBY1	ENST00000216029.8	c.-39+627A>G		intron_variant	Intron 1 of 4	1	NM_015373.4	ENSP00000216029.3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44616 AN: 151926 Hom.: 6633 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.281

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44661 AN: 152048 Hom.: 6643 Cov.: 32 AF XY: 0.294 AC XY: 21832 AN XY: 74322

African (AFR) AF: 0.288 AC: 11939 AN: 41456

American (AMR) AF: 0.236 AC: 3606 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 994 AN: 3466

East Asian (EAS) AF: 0.357 AC: 1847 AN: 5170

South Asian (SAS) AF: 0.282 AC: 1361 AN: 4828

European-Finnish (FIN) AF: 0.334 AC: 3534 AN: 10580

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20316 AN: 67974

Other (OTH) AF: 0.286 AC: 604 AN: 2112

Alfa AF: 0.298 Hom.: 917

Bravo AF: 0.285

Asia WGS AF: 0.322 AC: 1121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.65
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs2064088; hg19: chr22-39053382; COSMIC: COSV53264498; COSMIC: COSV53264498;