rs545634

chr1-15443607-G-Achr1-15443607-G-C

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: -0.694

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
CTRC	NM_007272.3	c.493+52G>A		intron_variant		ENST00000375949.5
CTRC	XM_011540550.2	c.493+52G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTRC	ENST00000375949.5	c.493+52G>A		intron_variant		1	NM_007272.3	P1
CTRC	ENST00000375943.6	c.*93+52G>A		intron_variant		1
CTRC	ENST00000483406.1	n.403+52G>A		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes AF: 0.0891 AC: 22330 AN: 250700 Hom.: 1098 AF XY: 0.0894 AC XY: 12123 AN XY: 135584

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 SAS exome AF: 0.0781

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

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0574

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.00176

Gnomad4 SAS exome AF: 0.0763

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0929

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

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0836

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.00385

Gnomad4 SAS AF: 0.0689

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.115

Alfa AF: 0.107 Hom.: 209

Bravo AF: 0.105

Asia WGS AF: 0.0620 AC: 215 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary pancreatitis Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Feb 28, 2020

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.014
Dann	Benign	0.51

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

Other links and lift over

dbSNP: rs545634; hg19: chr1-15770102;