rs199613498

Variant names:

• chr7-142749534-A-G
• rs199613498
• NM_002769.5:c.40+10A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-142749534-A-G
• chr7-142749534-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BS2_Supporting

The NM_002769.5(PRSS1):​c.40+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000571 in 1,613,912 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., cov: 35)
  • Exomes 𝑓: 0.00056 (5 hom.)
• Consequence: PRSS1 NM_002769.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.758

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]

TRB (HGNC:12155):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-142749534-A-G is Benign according to our data. Variant chr7-142749534-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 416606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 96 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 rank	MANE	Protein	UniProt
PRSS1	NM_002769.5	c.40+10A>G		intron_variant	Intron 1 of 4	ENST00000311737.12	NP_002760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS1	ENST00000311737.12	c.40+10A>G		intron_variant	Intron 1 of 4	1	NM_002769.5	ENSP00000308720.7
PRSS1	ENST00000486171.5	c.40+10A>G		intron_variant	Intron 1 of 5	5		ENSP00000417854.1
PRSS1	ENST00000485223.1	n.53+10A>G		intron_variant	Intron 1 of 1	2
PRSS1	ENST00000497041.1	n.44+10A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152092 Hom.: 0 Cov.: 35

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00101 AC: 253 AN: 251476 AF XY: 0.000964

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.0217

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000564 AC: 825 AN: 1461820 Hom.: 5 Cov.: 46 AF XY: 0.000595 AC XY: 433 AN XY: 727212

Gnomad4 AFR exome AF: 0.0000299 AC: 1 AN: 33478

Gnomad4 AMR exome AF: 0.0000447 AC: 2 AN: 44724

Gnomad4 ASJ exome AF: 0.0223 AC: 582 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39698

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 86258

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53418

Gnomad4 NFE exome AF: 0.000131 AC: 146 AN: 1111946

Gnomad4 Remaining exome AF: 0.00152 AC: 92 AN: 60394

GnomAD4 genome AF: 0.000631 AC: 96 AN: 152092 Hom.: 0 Cov.: 35 AF XY: 0.000687 AC XY: 51 AN XY: 74262

Gnomad4 AFR AF: 0.0000483 AC: 0.0000482695 AN: 0.0000482695

Gnomad4 AMR AF: 0.000459 AC: 0.000458655 AN: 0.000458655

Gnomad4 ASJ AF: 0.0193 AC: 0.0193195 AN: 0.0193195

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000206 AC: 0.000205792 AN: 0.000205792

Gnomad4 OTH AF: 0.00288 AC: 0.00287632 AN: 0.00287632

Alfa AF: 0.00255 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary pancreatitis Benign:2

Feb 14, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jan 16, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Oct 19, 2023

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	-0.88
CADD	Benign	0.24
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199613498; hg19: chr7-142457385;