Genetic Variant CTRC:c.640-35G>T (chr1-15445562-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_007272.3(CTRC):c.640-35G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,604,500 control chromosomes in the GnomAD database, including 107,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10025 hom., cov: 32)

Exomes 𝑓: 0.36 ( 97655 hom. )

Consequence

CTRC
NM_007272.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.145

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 (BayesDel_noAF=-0.86).

BP6

Variant 1-15445562-G-T is Benign according to our data. Variant chr1-15445562-G-T is described in ClinVar as [Benign]. Clinvar id is 439563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTRC	NM_007272.3 link	c.640-35G>T		intron_variant	Intron 6 of 7	ENST00000375949.5	NP_009203.2	Q99895
CTRC	XM_011540550.2 link	c.494-35G>T		intron_variant	Intron 5 of 6		XP_011538852.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CTRC	ENST00000375949.5 link	c.640-35G>T	intron_variant	Intron 6 of 7	1	NM_007272.3	ENSP00000365116.4	Q99895
CTRC	ENST00000375943.6 link	c.*94-35G>T	intron_variant	Intron 3 of 4	1		ENSP00000365110.2	Q68DR9
CTRC	ENST00000483406.1 link	n.404-35G>T	intron_variant	Intron 4 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54924

AN:

151910

Hom.:

10016

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.371

GnomAD3 exomes

AF:

0.360

AC:

89504

AN:

248758

Hom.:

16318

AF XY:

0.363

AC XY:

48907

AN XY:

134792

show subpopulations

Gnomad AFR exome

AF:

0.392

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.428

Gnomad EAS exome

AF:

0.236

Gnomad SAS exome

AF:

0.405

Gnomad FIN exome

AF:

0.276

Gnomad NFE exome

AF:

0.367

Gnomad OTH exome

AF:

0.380

GnomAD4 exome

AF:

0.364

AC:

528718

AN:

1452474

Hom.:

97655

Cov.:

AF XY:

0.365

AC XY:

263608

AN XY:

721940

show subpopulations

Gnomad4 AFR exome

AF:

0.389

Gnomad4 AMR exome

AF:

0.372

Gnomad4 ASJ exome

AF:

0.433

Gnomad4 EAS exome

AF:

0.278

Gnomad4 SAS exome

AF:

0.399

Gnomad4 FIN exome

AF:

0.280

Gnomad4 NFE exome

AF:

0.365

Gnomad4 OTH exome

AF:

0.373

GnomAD4 genome

AF:

0.362

AC:

54975

AN:

152026

Hom.:

10025

Cov.:

AF XY:

0.357

AC XY:

26513

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.386

Gnomad4 AMR

AF:

0.369

Gnomad4 ASJ

AF:

0.445

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.393

Gnomad4 FIN

AF:

0.274

Gnomad4 NFE

AF:

0.361

Gnomad4 OTH

AF:

0.373

Alfa

AF:

0.304

Hom.:

1614

Bravo

AF:

0.370

Asia WGS

AF:

0.318

AC:

1109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary pancreatitis

Benign:1

Apr 20, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.28

DANN

Benign

0.81

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