rs545634

Variant names:

• chr1-15443607-G-A
• rs545634
• NM_007272.3:c.493+52G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-15443607-G-A
• chr1-15443607-G-C

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.493+52G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 1,611,828 control chromosomes in the GnomAD database, including 8,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (906 hom., cov: 32)
  • Exomes 𝑓: 0.097 (7284 hom.)
• Consequence: CTRC NM_007272.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.694
• Publications: 12 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=-0.9).
• BP6: Variant 1-15443607-G-A is Benign according to our data. Variant chr1-15443607-G-A is described in ClinVar as Benign. ClinVar VariationId is 439564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTRC	NM_007272.3	c.493+52G>A		intron_variant	Intron 5 of 7	ENST00000375949.5	NP_009203.2
CTRC	XM_011540550.2	c.493+52G>A		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.493+52G>A		intron_variant	Intron 5 of 7	1	NM_007272.3	ENSP00000365116.4
CTRC	ENST00000375943.6	c.*93+52G>A		intron_variant	Intron 3 of 4	1		ENSP00000365110.2
CTRC	ENST00000483406.1	n.403+52G>A		intron_variant	Intron 4 of 5	5
CTRC	ENST00000476813.5	n.*67G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16097 AN: 152178 Hom.: 904 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.00384

Gnomad SAS AF: 0.0687

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.114

GnomAD2 exomes AF: 0.0891 AC: 22330 AN: 250700 AF XY: 0.0894

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.0545

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.00299

Gnomad FIN exome AF: 0.110

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.0947

GnomAD4 exome AF: 0.0969 AC: 141370 AN: 1459532 Hom.: 7284 Cov.: 31 AF XY: 0.0964 AC XY: 69989 AN XY: 726234

African (AFR) AF: 0.127 AC: 4260 AN: 33420

American (AMR) AF: 0.0574 AC: 2565 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 3023 AN: 26112

East Asian (EAS) AF: 0.00176 AC: 70 AN: 39688

South Asian (SAS) AF: 0.0763 AC: 6581 AN: 86196

European-Finnish (FIN) AF: 0.112 AC: 5925 AN: 52920

Middle Eastern (MID) AF: 0.104 AC: 599 AN: 5764

European-Non Finnish (NFE) AF: 0.102 AC: 112742 AN: 1110378

Other (OTH) AF: 0.0929 AC: 5605 AN: 60342

GnomAD4 genome AF: 0.106 AC: 16109 AN: 152296 Hom.: 906 Cov.: 32 AF XY: 0.105 AC XY: 7783 AN XY: 74458

African (AFR) AF: 0.127 AC: 5292 AN: 41548

American (AMR) AF: 0.0836 AC: 1280 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3472

East Asian (EAS) AF: 0.00385 AC: 20 AN: 5192

South Asian (SAS) AF: 0.0689 AC: 333 AN: 4830

European-Finnish (FIN) AF: 0.113 AC: 1196 AN: 10602

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7269 AN: 68028

Other (OTH) AF: 0.115 AC: 244 AN: 2116

Alfa AF: 0.104 Hom.: 338

Bravo AF: 0.105

Asia WGS AF: 0.0620 AC: 215 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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

Feb 28, 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	-0.90
CADD	Benign	0.014
DANN	Benign	0.51
PhyloP100		-0.69
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: rs545634; hg19: chr1-15770102;