chr22-38673176-T-C

Variant names:

• chr22-38673176-T-C
• rs3747174
• NM_015373.4:c.321T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015373.4(CBY1):​c.321T>C​(p.Ala107Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 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
• Publications: 30 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
CBY1	NM_015373.4	c.321T>C	p.Ala107Ala	synonymous_variant	Exon 5 of 5	ENST00000216029.8	NP_056188.1
CBY1	NM_001002880.4	c.321T>C	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>C	p.Ala107Ala	synonymous_variant	Exon 5 of 5	1	NM_015373.4	ENSP00000216029.3

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

GnomAD2 exomes AF: 0.286 AC: 71899 AN: 251220 AF XY: 0.287

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 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

African (AFR) AF: 0.295 AC: 9834 AN: 33346

American (AMR) AF: 0.215 AC: 9599 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 7372 AN: 26078

East Asian (EAS) AF: 0.355 AC: 14060 AN: 39644

South Asian (SAS) AF: 0.267 AC: 22976 AN: 86110

European-Finnish (FIN) AF: 0.336 AC: 17933 AN: 53374

Middle Eastern (MID) AF: 0.287 AC: 1651 AN: 5756

European-Non Finnish (NFE) AF: 0.285 AC: 315699 AN: 1106108

Other (OTH) AF: 0.284 AC: 17083 AN: 60172

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

African (AFR) AF: 0.291 AC: 12078 AN: 41468

American (AMR) AF: 0.237 AC: 3614 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3464

East Asian (EAS) AF: 0.359 AC: 1858 AN: 5176

South Asian (SAS) AF: 0.277 AC: 1333 AN: 4816

European-Finnish (FIN) AF: 0.333 AC: 3518 AN: 10560

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20257 AN: 67974

Other (OTH) AF: 0.285 AC: 602 AN: 2112

Alfa AF: 0.284 Hom.: 5792

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
PhyloP100		-4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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