1-175006836-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014412.3(CACYBP):ā€‹c.327A>Gā€‹(p.Thr109Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,527,972 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.017 ( 53 hom., cov: 32)
Exomes š‘“: 0.0017 ( 71 hom. )

Consequence

CACYBP
NM_014412.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.846
Variant links:
Genes affected
CACYBP (HGNC:30423): (calcyclin binding protein) The protein encoded by this gene is a calcyclin binding protein. It may be involved in calcium-dependent ubiquitination and subsequent proteosomal degradation of target proteins. It probably serves as a molecular bridge in ubiquitin E3 complexes and participates in the ubiquitin-mediated degradation of beta-catenin. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 1-175006836-A-G is Benign according to our data. Variant chr1-175006836-A-G is described in ClinVar as [Benign]. Clinvar id is 775625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.846 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CACYBPNM_014412.3 linkuse as main transcriptc.327A>G p.Thr109Thr synonymous_variant 3/6 ENST00000367679.7 NP_055227.1 Q9HB71-1A0A024R904
CACYBPNM_001007214.1 linkuse as main transcriptc.198A>G p.Thr66Thr synonymous_variant 3/6 NP_001007215.1 Q9HB71-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CACYBPENST00000367679.7 linkuse as main transcriptc.327A>G p.Thr109Thr synonymous_variant 3/61 NM_014412.3 ENSP00000356652.2 Q9HB71-1

Frequencies

GnomAD3 genomes
AF:
0.0166
AC:
2533
AN:
152218
Hom.:
53
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0582
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00537
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.0139
GnomAD3 exomes
AF:
0.00431
AC:
1082
AN:
251014
Hom.:
30
AF XY:
0.00304
AC XY:
412
AN XY:
135684
show subpopulations
Gnomad AFR exome
AF:
0.0601
Gnomad AMR exome
AF:
0.00238
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000881
Gnomad OTH exome
AF:
0.00147
GnomAD4 exome
AF:
0.00173
AC:
2375
AN:
1375636
Hom.:
71
Cov.:
22
AF XY:
0.00152
AC XY:
1048
AN XY:
689514
show subpopulations
Gnomad4 AFR exome
AF:
0.0606
Gnomad4 AMR exome
AF:
0.00298
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000189
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000803
Gnomad4 OTH exome
AF:
0.00379
GnomAD4 genome
AF:
0.0166
AC:
2535
AN:
152336
Hom.:
53
Cov.:
32
AF XY:
0.0161
AC XY:
1198
AN XY:
74506
show subpopulations
Gnomad4 AFR
AF:
0.0581
Gnomad4 AMR
AF:
0.00529
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.0137
Alfa
AF:
0.00801
Hom.:
23
Bravo
AF:
0.0196
Asia WGS
AF:
0.00346
AC:
12
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
CADD
Benign
9.0
DANN
Benign
0.86

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.

Other links and lift over

dbSNP: rs1802325; hg19: chr1-174975972; API