1-15440540-C-T

Variant names:

• chr1-15440540-C-T
• rs497078
• NM_007272.3:c.180C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -3.90
• Publications: 48 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007272.3. 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.180C>T	p.Gly60Gly	synonymous	Exon 3 of 8	NP_009203.2	Q99895

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTRC	ENST00000375949.5	TSL:1 MANE Select	c.180C>T	p.Gly60Gly	synonymous	Exon 3 of 8	ENSP00000365116.4	Q99895
	CTRC	ENST00000375943.6	TSL:1	c.41-1907C>T		intron	N/A	ENSP00000365110.2	Q68DR9
	CTRC	ENST00000483406.1	TSL:5	n.90C>T		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17332 AN: 152088 Hom.: 1053 Cov.: 32

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

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.: 34 AF XY: 0.0973 AC XY: 70727 AN XY: 727128

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: 66 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

GnomAD4 genome AF: 0.114 AC: 17354 AN: 152206 Hom.: 1056 Cov.: 32 AF XY: 0.112 AC XY: 8368 AN XY: 74428

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: 19 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: 31 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7273 AN: 68004

Other (OTH) AF: 0.121 AC: 256 AN: 2108

Alfa AF: 0.0978 Hom.: 421

Bravo AF: 0.116

EpiCase AF: 0.108

EpiControl AF: 0.107

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.17
DANN	Benign	0.78
PhyloP100		-3.9
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs497078; hg19: chr1-15767036; COSMIC: COSV65621791;