1-15442501-C-T

Position:

chr1-15442501-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000375943.6(CTRC):c.95C>T(p.Thr32Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,614,106 control chromosomes in the GnomAD database, including 1,205 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict 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. T32T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.025 ( 77 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1128 hom. )

Consequence

CTRC
ENST00000375943.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -6.81

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026253164).

BP6

Variant 1-15442501-C-T is Benign according to our data. Variant chr1-15442501-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-15442501-C-T is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTRC	NM_007272.3 linkuse as main transcript	c.285C>T	p.Asp95=	synonymous_variant	4/8	ENST00000375949.5
CTRC	XM_011540550.2 linkuse as main transcript	c.285C>T	p.Asp95=	synonymous_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CTRC	ENST00000375943.6 linkuse as main transcript	c.95C>T	p.Thr32Met	missense_variant	2/5	1
CTRC	ENST00000375949.5 linkuse as main transcript	c.285C>T	p.Asp95=	synonymous_variant	4/8	1	NM_007272.3	P1
CTRC	ENST00000476813.5 linkuse as main transcript	n.107C>T		non_coding_transcript_exon_variant	2/3	3
CTRC	ENST00000483406.1 linkuse as main transcript	n.195C>T		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes

AF:

0.0251

AC:

3823

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00637

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.0307

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.0506

Gnomad SAS

AF:

0.0410

Gnomad FIN

AF:

0.00980

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0346

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0334

AC:

8401

AN:

251370

Hom.:

186

AF XY:

0.0346

AC XY:

4707

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00671

Gnomad AMR exome

AF:

0.0383

Gnomad ASJ exome

AF:

0.0222

Gnomad EAS exome

AF:

0.0415

Gnomad SAS exome

AF:

0.0492

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0351

Gnomad OTH exome

AF:

0.0336

GnomAD4 exome

AF:

0.0354

AC:

51813

AN:

1461824

Hom.:

1128

Cov.:

AF XY:

0.0358

AC XY:

26050

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00576

Gnomad4 AMR exome

AF:

0.0359

Gnomad4 ASJ exome

AF:

0.0238

Gnomad4 EAS exome

AF:

0.0797

Gnomad4 SAS exome

AF:

0.0468

Gnomad4 FIN exome

AF:

0.0140

Gnomad4 NFE exome

AF:

0.0352

Gnomad4 OTH exome

AF:

0.0336

GnomAD4 genome

AF:

0.0251

AC:

3827

AN:

152282

Hom.:

Cov.:

AF XY:

0.0242

AC XY:

1802

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00635

Gnomad4 AMR

AF:

0.0307

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.0509

Gnomad4 SAS

AF:

0.0410

Gnomad4 FIN

AF:

0.00980

Gnomad4 NFE

AF:

0.0346

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0308

Hom.:

Bravo

AF:

0.0250

TwinsUK

AF:

0.0361

AC:

134

ALSPAC

AF:

0.0355

AC:

137

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.0345

AC:

297

ExAC

AF:

0.0338

AC:

4107

EpiCase

AF:

0.0368

EpiControl

AF:

0.0364

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary pancreatitis

Benign:4

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Dec 31, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jan 25, 2016	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

This variant is associated with the following publications: (PMID: 18172691, 23135764) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.37

DANN

Benign

0.47

DEOGEN2

Benign

0.10

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.036

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

D;N

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.076

Vest4

0.066

ClinPred

0.029

GERP RS

-6.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over