22-38673176-T-G

Variant names:

• chr22-38673176-T-G
• NM_015373.4:c.321T>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_015373.4(CBY1):​c.321T>G​(p.Ala107Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CBY1 NM_015373.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.93

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]

ENSG00000228274 (HGNC:56758): (TOMM22 divergent transcript)

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-4.93 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBY1	NM_015373.4	c.321T>G	p.Ala107Ala	synonymous_variant	Exon 5 of 5	ENST00000216029.8	NP_056188.1
CBY1	NM_001002880.4	c.321T>G	p.Ala107Ala	synonymous_variant	Exon 6 of 6		NP_001002880.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBY1	ENST00000216029.8	c.321T>G	p.Ala107Ala	synonymous_variant	Exon 5 of 5	1	NM_015373.4	ENSP00000216029.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458848 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725890

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.090
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr22-39069181;