chr1-15440516-C-T

Position:

chr1-15440516-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_007272.3(CTRC):c.156C>T(p.Asn52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,614,206 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 21 hom., cov: 31)

Exomes 𝑓: 0.00080 ( 24 hom. )

Consequence

CTRC
NM_007272.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -5.31

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-15440516-C-T is Benign according to our data. Variant chr1-15440516-C-T is described in ClinVar as [Benign]. Clinvar id is 292908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.31 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00772 (1176/152344) while in subpopulation AFR AF= 0.0261 (1084/41584). AF 95% confidence interval is 0.0248. There are 21 homozygotes in gnomad4. There are 569 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTRC	NM_007272.3 linkuse as main transcript	c.156C>T	p.Asn52=	synonymous_variant	3/8	ENST00000375949.5
CTRC	XM_011540550.2 linkuse as main transcript	c.156C>T	p.Asn52=	synonymous_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CTRC	ENST00000375949.5 linkuse as main transcript	c.156C>T	p.Asn52=	synonymous_variant	3/8	1	NM_007272.3	P1
CTRC	ENST00000375943.6 linkuse as main transcript	c.41-1931C>T		intron_variant		1
CTRC	ENST00000483406.1 linkuse as main transcript	n.66C>T		non_coding_transcript_exon_variant	2/6	5
CTRC	ENST00000476813.5 linkuse as main transcript	n.53-1931C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00771

AC:

1173

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00191

AC:

479

AN:

251406

Hom.:

AF XY:

0.00133

AC XY:

181

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0261

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000801

AC:

1171

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000707

AC XY:

514

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0283

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000405

Gnomad4 OTH exome

AF:

0.00166

GnomAD4 genome

AF:

0.00772

AC:

1176

AN:

152344

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

569

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0261

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00455

Hom.:

Bravo

AF:

0.00903

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Ambry Genetics	Sep 11, 2014	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 09, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.093

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over