chr1-15440540-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007272.3(CTRC):c.180C>T(p.Gly60Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 1,613,874 control chromosomes in the GnomAD database, including 8,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G60G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.11 ( 1056 hom., cov: 32)

Exomes 𝑓: 0.098 ( 7515 hom. )

Consequence

CTRC
NM_007272.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.90

Publications

47 publications found

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]

CTRC Gene-Disease associations (from GenCC):

hereditary chronic pancreatitis
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

CTRC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-15440540-C-T is Benign according to our data. Variant chr1-15440540-C-T is described in ClinVar as Benign. ClinVar VariationId is 260156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTRC	NM_007272.3 link	c.180C>T	p.Gly60Gly	synonymous_variant	Exon 3 of 8	ENST00000375949.5	NP_009203.2	Q99895
CTRC	XM_011540550.2 link	c.180C>T	p.Gly60Gly	synonymous_variant	Exon 3 of 7		XP_011538852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CTRC	ENST00000375949.5 link	c.180C>T	p.Gly60Gly	synonymous_variant	Exon 3 of 8	1	NM_007272.3	ENSP00000365116.4	Q99895
CTRC	ENST00000375943.6 link	c.41-1907C>T		intron_variant	Intron 1 of 4	1		ENSP00000365110.2	Q68DR9
CTRC	ENST00000483406.1 link	n.90C>T		non_coding_transcript_exon_variant	Exon 2 of 6	5
CTRC	ENST00000476813.5 link	n.53-1907C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17332

AN:

152088

Hom.:

1053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.0863

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.0683

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.121

GnomAD2 exomes

AF:

0.0910

AC:

22857

AN:

251208

AF XY:

0.0908

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.0555

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.00283

Gnomad FIN exome

AF:

0.109

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.0957

GnomAD4 exome

AF:

0.0979

AC:

143102

AN:

1461668

Hom.:

7515

Cov.:

AF XY:

0.0973

AC XY:

70727

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.158

AC:

5296

AN:

33472

American (AMR)

AF:

0.0584

AC:

2612

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

3022

AN:

26136

East Asian (EAS)

AF:

0.00166

AC:

AN:

39700

South Asian (SAS)

AF:

0.0764

AC:

6585

AN:

86232

European-Finnish (FIN)

AF:

0.112

AC:

5964

AN:

53404

Middle Eastern (MID)

AF:

0.105

AC:

608

AN:

5766

European-Non Finnish (NFE)

AF:

0.102

AC:

113234

AN:

1111860

Other (OTH)

AF:

0.0946

AC:

5715

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

7494

14988

22482

29976

37470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4022

8044

12066

16088

20110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.114

AC:

17354

AN:

152206

Hom.:

1056

Cov.:

AF XY:

0.112

AC XY:

8368

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.156

AC:

6493

AN:

41514

American (AMR)

AF:

0.0861

AC:

1317

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

358

AN:

3472

East Asian (EAS)

AF:

0.00366

AC:

AN:

5186

South Asian (SAS)

AF:

0.0685

AC:

330

AN:

4816

European-Finnish (FIN)

AF:

0.112

AC:

1191

AN:

10612

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.107

AC:

7273

AN:

68004

Other (OTH)

AF:

0.121

AC:

256

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

801

1603

2404

3206

4007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0978

Hom.:

421

Bravo

AF:

0.116

EpiCase

AF:

0.108

EpiControl

AF:

0.107

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary pancreatitis

Benign:4

Mar 12, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:2

Dec 28, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.17

(source)

DANN

Benign

0.78

PhyloP100

-3.9

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over