1-15445562-G-T

Variant names:

• chr1-15445562-G-T
• rs10927786
• NM_007272.3:c.640-35G>T

Variant summary

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

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.145
• Publications: 7 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 (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 VariationId 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	c.640-35G>T		intron_variant	Intron 6 of 7	ENST00000375949.5	NP_009203.2
CTRC	XM_011540550.2	c.494-35G>T		intron_variant	Intron 5 of 6		XP_011538852.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54924 AN: 151910 Hom.: 10016 Cov.: 32

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

GnomAD2 exomes AF: 0.360 AC: 89504 AN: 248758 AF XY: 0.363

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 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.: 33 AF XY: 0.365 AC XY: 263608 AN XY: 721940

African (AFR) AF: 0.389 AC: 12947 AN: 33300

American (AMR) AF: 0.372 AC: 16621 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 11287 AN: 26062

East Asian (EAS) AF: 0.278 AC: 10982 AN: 39574

South Asian (SAS) AF: 0.399 AC: 34339 AN: 86136

European-Finnish (FIN) AF: 0.280 AC: 14814 AN: 52924

Middle Eastern (MID) AF: 0.428 AC: 2423 AN: 5666

European-Non Finnish (NFE) AF: 0.365 AC: 402928 AN: 1104158

Other (OTH) AF: 0.373 AC: 22377 AN: 60006

GnomAD4 genome AF: 0.362 AC: 54975 AN: 152026 Hom.: 10025 Cov.: 32 AF XY: 0.357 AC XY: 26513 AN XY: 74326

African (AFR) AF: 0.386 AC: 15995 AN: 41472

American (AMR) AF: 0.369 AC: 5636 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1542 AN: 3468

East Asian (EAS) AF: 0.240 AC: 1241 AN: 5170

South Asian (SAS) AF: 0.393 AC: 1892 AN: 4820

European-Finnish (FIN) AF: 0.274 AC: 2902 AN: 10584

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24521 AN: 67926

Other (OTH) AF: 0.373 AC: 785 AN: 2104

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

Submissions by phenotype

not provided Benign:2

Jun 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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
PhyloP100		-0.14
Mutation Taster		=100/0	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: rs10927786; hg19: chr1-15772057; COSMIC: COSV65621428; COSMIC: COSV65621428;