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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hereditary chronic pancreatitis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, PanelApp Australia, Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• malignant pancreatic neoplasm

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp

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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002769.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	NM_002769.5	MANE Select	c.40+10A>G		intron	N/A	NP_002760.1
	PRSS1	NR_172947.1		n.53+10A>G		intron	N/A
	PRSS1	NR_172948.1		n.53+10A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	ENST00000311737.12	TSL:1 MANE Select	c.40+10A>G		intron	N/A	ENSP00000308720.7
	PRSS1	ENST00000486171.5	TSL:5	c.40+10A>G		intron	N/A	ENSP00000417854.1
	PRSS1	ENST00000492062.2	TSL:2	c.40+10A>G		intron	N/A	ENSP00000419912.2

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

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0223 AC: 582 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.000131 AC: 146 AN: 1111946

Other (OTH) 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

African (AFR) AF: 0.0000483 AC: 2 AN: 41434

American (AMR) AF: 0.000459 AC: 7 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68030

Other (OTH) AF: 0.00288 AC: 6 AN: 2086

Alfa AF: 0.00255 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary pancreatitis (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.24
DANN	Benign	0.53
PhyloP100		-0.76
PromoterAI		0.017	Neutral

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

Other links and lift over

dbSNP: rs199613498; hg19: chr7-142457385;