chr7-142752860-C-T

Position:

chr7-142752860-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBS1BS2_Supporting

The NM_002769.5(PRSS1):c.592-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,613,518 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 41)

Exomes 𝑓: 0.0026 ( 35 hom. )

Consequence

PRSS1
NM_002769.5 splice_region, intron

Scores

Splicing: ADA: 0.0003019

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0310

Variant links:

Genes affected

PRSS1 (HGNC:9475): (serine protease 1) This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Mutations in this gene are associated with hereditary pancreatitis. This gene and several other trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7. [provided by RefSeq, Jul 2008]

PRSS1 links:

TRB (HGNC:):

TRB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

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

BP6

Variant 7-142752860-C-T is Benign according to our data. Variant chr7-142752860-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 416610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-142752860-C-T is described in Lovd as [Likely_benign]. Variant chr7-142752860-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00264 (3860/1461202) while in subpopulation MID AF= 0.0339 (195/5756). AF 95% confidence interval is 0.03. There are 35 homozygotes in gnomad4_exome. There are 2326 alleles in male gnomad4_exome subpopulation. Median coverage is 48. This position pass quality control queck.

BS2

High AC in GnomAd4 at 312 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS1	NM_002769.5 linkuse as main transcript	c.592-8C>T		splice_region_variant, intron_variant		ENST00000311737.12	NP_002760.1	P07477

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PRSS1	ENST00000311737.12 linkuse as main transcript	c.592-8C>T	splice_region_variant, intron_variant	1	NM_002769.5	ENSP00000308720.7	P07477
PRSS1	ENST00000486171.5 linkuse as main transcript	c.634-8C>T	splice_region_variant, intron_variant	5		ENSP00000417854.1	E7EQ64
PRSS1	ENST00000492062.1 linkuse as main transcript	c.425-8C>T	splice_region_variant, intron_variant	2		ENSP00000419912.2	H0Y8D1
PRSS1	ENST00000463701.1 linkuse as main transcript	n.1056-8C>T	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

312

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00225

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00356

AC:

894

AN:

251470

Hom.:

AF XY:

0.00445

AC XY:

605

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00645

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0148

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00246

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00264

AC:

3860

AN:

1461202

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

2326

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.000927

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.00689

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0151

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00163

Gnomad4 OTH exome

AF:

0.00391

GnomAD4 genome

AF:

0.00205

AC:

312

AN:

152316

Hom.:

Cov.:

AF XY:

0.00213

AC XY:

159

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0150

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00225

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00196

Hom.:

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00373

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

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 01, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Sep 14, 2015	This alteration is classified as likely 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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 04, 2020	This variant is associated with the following publications: (PMID: 27264265, 24458023, 28502372, 30134826) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.6

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00030

dbscSNV1_RF

Benign

0.044

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