Variant chr22-38673176-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.93

Variant links:

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 links:

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

TOMM22-DT links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
CBY1	NM_015373.4 linkuse as main transcript	c.321T>C	p.Ala107=	synonymous_variant	5/5	ENST00000216029.8	NP_056188.1
CBY1	NM_001002880.4 linkuse as main transcript	c.321T>C	p.Ala107=	synonymous_variant	6/6		NP_001002880.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBY1	ENST00000216029.8 linkuse as main transcript	c.321T>C	p.Ala107=	synonymous_variant	5/5	1	NM_015373.4	ENSP00000216029	P1
TOMM22-DT	ENST00000431924.3 linkuse as main transcript	n.136-4851A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44676

AN:

151928

Hom.:

6660

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.286

AC XY:

206765

AN XY:

724188

show subpopulations

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.:

AF XY:

0.294

AC XY:

21859

AN XY:

74312

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over