rs3747174

chr22-38673176-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015373.4(CBY1):c.321T>C(p.Ala107=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,607,316 control chromosomes in the GnomAD database, including 67,420 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 (6670 hom., cov: 31)
  • Exomes 𝑓: 0.29 (60750 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]

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

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-4.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CBY1	NM_015373.4	c.321T>C	p.Ala107=	synonymous_variant	5/5	ENST00000216029.8
CBY1	NM_001002880.4	c.321T>C	p.Ala107=	synonymous_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CBY1	ENST00000216029.8	c.321T>C	p.Ala107=	synonymous_variant	5/5	1	NM_015373.4	P1
TOMM22-DT	ENST00000431924.3	n.136-4851A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44676 AN: 151928 Hom.: 6660 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.280

GnomAD3 exomes AF: 0.286 AC: 71899 AN: 251220 Hom.: 10579 AF XY: 0.287 AC XY: 38967 AN XY: 135770

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.369

Gnomad SAS exome AF: 0.269

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.288

Gnomad OTH exome AF: 0.298

GnomAD4 exome AF: 0.286 AC: 416207 AN: 1455270 Hom.: 60750 Cov.: 29 AF XY: 0.286 AC XY: 206765 AN XY: 724188

Gnomad4 AFR exome AF: 0.295

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.355

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.336

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.294 AC: 44719 AN: 152046 Hom.: 6670 Cov.: 31 AF XY: 0.294 AC XY: 21859 AN XY: 74312

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.285

Alfa AF: 0.282 Hom.: 4381

Bravo AF: 0.285

Asia WGS AF: 0.319 AC: 1113 AN: 3478

EpiCase AF: 0.289

EpiControl AF: 0.283

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.084
Dann	Benign	0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs3747174; hg19: chr22-39069181; COSMIC: COSV53264310; COSMIC: COSV53264310;