rs386134264

Variant names:

• chr7-142749451-GTCC-G
• rs386134264

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The variant allele was found at a frequency of 0.000291 in 1,613,274 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: TRB intragenic
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:4
• Conservation: PhyloP100: -0.129
• Publications: 0 publications found

Genes affected

TRB (HGNC:12155):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP6: Variant 7-142749451-GTCC-G is Benign according to our data. Variant chr7-142749451-GTCC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 36703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000311737.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	NM_002769.5	MANE Select	c.-33_-31delTCC		upstream_gene	N/A	NP_002760.1
	PRSS1	NR_172947.1		n.-20_-18delTCC		upstream_gene	N/A
	PRSS1	NR_172948.1		n.-20_-18delTCC		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	ENST00000311737.12	TSL:1 MANE Select	c.-33_-31delTCC		upstream_gene	N/A	ENSP00000308720.7
	PRSS1	ENST00000486171.5	TSL:5	c.-33_-31delTCC		upstream_gene	N/A	ENSP00000417854.1
	PRSS1	ENST00000492062.2	TSL:2	c.-33_-31delTCC		upstream_gene	N/A	ENSP00000419912.2

Frequencies

GnomAD3 genomes AF: 0.00124 AC: 188 AN: 152084 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000382 AC: 96 AN: 251444 AF XY: 0.000258

Gnomad AFR exome AF: 0.00406

Gnomad AMR exome AF: 0.000491

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000192 AC: 280 AN: 1461072 Hom.: 0 AF XY: 0.000162 AC XY: 118 AN XY: 726942

African (AFR) AF: 0.00493 AC: 165 AN: 33448

American (AMR) AF: 0.000760 AC: 34 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.0000378 AC: 42 AN: 1111290

Other (OTH) AF: 0.000563 AC: 34 AN: 60370

GnomAD4 genome AF: 0.00124 AC: 189 AN: 152202 Hom.: 2 Cov.: 32 AF XY: 0.00106 AC XY: 79 AN XY: 74408

African (AFR) AF: 0.00412 AC: 171 AN: 41536

American (AMR) AF: 0.000851 AC: 13 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000719 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
1	-	2	Hereditary pancreatitis (3)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.13

Splicing

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

Other links and lift over

dbSNP: rs386134264; hg19: chr7-142457302;