1-15442501-C-T

Variant names:

• chr1-15442501-C-T
• rs41307798
• ENST00000375943.6:c.95C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 12/16 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -6.81
• Publications: 6 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 260157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375943.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTRC	NM_007272.3	MANE Select	c.285C>T	p.Asp95Asp	synonymous	Exon 4 of 8	NP_009203.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTRC	ENST00000375943.6	TSL:1	c.95C>T	p.Thr32Met	missense	Exon 2 of 5	ENSP00000365110.2
	CTRC	ENST00000375949.5	TSL:1 MANE Select	c.285C>T	p.Asp95Asp	synonymous	Exon 4 of 8	ENSP00000365116.4
	CTRC	ENST00000476813.5	TSL:3	n.107C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3823 AN: 152164 Hom.: 76 Cov.: 32

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

GnomAD2 exomes AF: 0.0334 AC: 8401 AN: 251370 AF XY: 0.0346

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 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.: 32 AF XY: 0.0358 AC XY: 26050 AN XY: 727216

African (AFR) AF: 0.00576 AC: 193 AN: 33478

American (AMR) AF: 0.0359 AC: 1606 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0238 AC: 621 AN: 26134

East Asian (EAS) AF: 0.0797 AC: 3163 AN: 39692

South Asian (SAS) AF: 0.0468 AC: 4038 AN: 86252

European-Finnish (FIN) AF: 0.0140 AC: 747 AN: 53412

Middle Eastern (MID) AF: 0.0544 AC: 314 AN: 5768

European-Non Finnish (NFE) AF: 0.0352 AC: 39102 AN: 1111980

Other (OTH) AF: 0.0336 AC: 2029 AN: 60394

GnomAD4 genome AF: 0.0251 AC: 3827 AN: 152282 Hom.: 77 Cov.: 32 AF XY: 0.0242 AC XY: 1802 AN XY: 74462

African (AFR) AF: 0.00635 AC: 264 AN: 41548

American (AMR) AF: 0.0307 AC: 470 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3472

East Asian (EAS) AF: 0.0509 AC: 263 AN: 5164

South Asian (SAS) AF: 0.0410 AC: 198 AN: 4830

European-Finnish (FIN) AF: 0.00980 AC: 104 AN: 10614

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0346 AC: 2355 AN: 68030

Other (OTH) AF: 0.0265 AC: 56 AN: 2112

Alfa AF: 0.0331 Hom.: 195

Bravo AF: 0.0250

TwinsUK AF: 0.0361 AC: 134

ALSPAC AF: 0.0355 AC: 137

ESP6500AA AF: 0.00590 AC: 26

ESP6500EA AF: 0.0345 AC: 297

ExAC AF: 0.0338 AC: 4107

EpiCase AF: 0.0368

EpiControl AF: 0.0364

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Hereditary pancreatitis (4)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.37
DANN	Benign	0.47
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.036	N
MetaRNN	Benign	0.0026	T
MetaSVM	Benign	-0.95	T
PhyloP100		-6.8
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.076
Vest4		0.066
ClinPred		0.029	T
GERP RS		-6.2
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41307798; hg19: chr1-15768997; COSMIC: COSV65621977;