rs497078

Variant summary

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

The ENST00000375949.5(CTRC):​c.180C>A​(p.Gly60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,614,058 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G60G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.014 ( 60 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 63 hom. )

Consequence

CTRC
ENST00000375949.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -3.90
Variant links:
Genes affected
CTRC (HGNC:2523): (chymotrypsin C) This gene encodes a member of the peptidase S1 family. The encoded protein is a serum calcium-decreasing factor that has chymotrypsin-like protease activity. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined. [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=-0.73).
BP6
Variant 1-15440540-C-A is Benign according to our data. Variant chr1-15440540-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 240763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.9 with no splicing effect.
BA1
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CTRCNM_007272.3 linkuse as main transcriptc.180C>A p.Gly60= synonymous_variant 3/8 ENST00000375949.5 NP_009203.2
CTRCXM_011540550.2 linkuse as main transcriptc.180C>A p.Gly60= synonymous_variant 3/7 XP_011538852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CTRCENST00000375949.5 linkuse as main transcriptc.180C>A p.Gly60= synonymous_variant 3/81 NM_007272.3 ENSP00000365116 P1
CTRCENST00000375943.6 linkuse as main transcriptc.41-1907C>A intron_variant 1 ENSP00000365110
CTRCENST00000483406.1 linkuse as main transcriptn.90C>A non_coding_transcript_exon_variant 2/65
CTRCENST00000476813.5 linkuse as main transcriptn.53-1907C>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0140
AC:
2126
AN:
152106
Hom.:
59
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0489
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00472
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00911
GnomAD3 exomes
AF:
0.00368
AC:
925
AN:
251208
Hom.:
18
AF XY:
0.00260
AC XY:
353
AN XY:
135796
show subpopulations
Gnomad AFR exome
AF:
0.0517
Gnomad AMR exome
AF:
0.00197
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.00146
AC:
2131
AN:
1461834
Hom.:
63
Cov.:
34
AF XY:
0.00124
AC XY:
899
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.0538
Gnomad4 AMR exome
AF:
0.00248
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000270
Gnomad4 OTH exome
AF:
0.00286
GnomAD4 genome
AF:
0.0141
AC:
2140
AN:
152224
Hom.:
60
Cov.:
32
AF XY:
0.0140
AC XY:
1040
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0491
Gnomad4 AMR
AF:
0.00471
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00901
Alfa
AF:
0.000313
Hom.:
258
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hereditary pancreatitis Benign:4Other:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 20, 2014This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesNov 17, 2023- -
association, no assertion criteria providedliterature onlyGeneReviewsMar 13, 2014- -
not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 22, 2018- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.016
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs497078; hg19: chr1-15767036; API