rs75456156

chr1-15446672-T-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.*83T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00493 in 1,510,036 control chromosomes in the GnomAD database, including 338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (183 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (155 hom.)
• Consequence: CTRC NM_007272.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.15

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=-0.91).
• BP6: Variant 1-15446672-T-C is Benign according to our data. Variant chr1-15446672-T-C is described in ClinVar as [Benign]. Clinvar id is 368835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTRC	NM_007272.3	c.*83T>C		3_prime_UTR_variant	8/8	ENST00000375949.5
CTRC	XM_011540550.2	c.744T>C	p.Cys248=	synonymous_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTRC	ENST00000375949.5	c.*83T>C		3_prime_UTR_variant	8/8	1	NM_007272.3	P1
CTRC	ENST00000375943.6	c.*344T>C		3_prime_UTR_variant	5/5	1
CTRC	ENST00000483406.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3850 AN: 152184 Hom.: 183 Cov.: 32

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00650 AC: 1629 AN: 250478 Hom.: 66 AF XY: 0.00471 AC XY: 638 AN XY: 135438

Gnomad AFR exome AF: 0.0906

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000393

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00264 AC: 3589 AN: 1357734 Hom.: 155 Cov.: 21 AF XY: 0.00233 AC XY: 1584 AN XY: 681172

Gnomad4 AFR exome AF: 0.0914

Gnomad4 AMR exome AF: 0.00348

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000309

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000160

Gnomad4 OTH exome AF: 0.00588

GnomAD4 genome AF: 0.0253 AC: 3860 AN: 152302 Hom.: 183 Cov.: 32 AF XY: 0.0243 AC XY: 1811 AN XY: 74470

Gnomad4 AFR AF: 0.0877

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0151 Hom.: 26

Bravo AF: 0.0291

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary pancreatitis Benign:4

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Nov 08, 2022	- -
Benign, criteria provided, single submitter	curation	Sema4, Sema4	Dec 09, 2019	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

This variant is associated with the following publications: (PMID: 18172691) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.34
Dann	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs75456156; hg19: chr1-15773167;