7-142749281-A-C

Variant names:

• chr7-142749281-A-C
• rs4726576

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The variant allele was found at a frequency of 0.555 in 145,756 control chromosomes in the GnomAD database, including 21,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.56 (21910 hom., cov: 29)
• Consequence: TRB intragenic
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.05
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-142749281-A-C is Benign according to our data. Variant chr7-142749281-A-C is described in ClinVar as Benign. ClinVar VariationId is 1169050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS1	NM_002769.5	c.-204A>C		upstream_gene_variant		ENST00000311737.12	NP_002760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS1	ENST00000311737.12	c.-204A>C		upstream_gene_variant		1	NM_002769.5	ENSP00000308720.7

Frequencies

GnomAD3 genomes AF: 0.555 AC: 80858 AN: 145652 Hom.: 21898 Cov.: 29

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.441

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.553

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.555 AC: 80911 AN: 145756 Hom.: 21910 Cov.: 29 AF XY: 0.550 AC XY: 39201 AN XY: 71286

African (AFR) AF: 0.560 AC: 20239 AN: 36152

American (AMR) AF: 0.588 AC: 8804 AN: 14984

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 1996 AN: 3442

East Asian (EAS) AF: 0.228 AC: 1159 AN: 5080

South Asian (SAS) AF: 0.317 AC: 1479 AN: 4668

European-Finnish (FIN) AF: 0.606 AC: 6340 AN: 10470

Middle Eastern (MID) AF: 0.440 AC: 125 AN: 284

European-Non Finnish (NFE) AF: 0.578 AC: 39170 AN: 67724

Other (OTH) AF: 0.547 AC: 1126 AN: 2058

Alfa AF: 0.513 Hom.: 2873

Asia WGS AF: 0.275 AC: 962 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary pancreatitis Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.022
DANN	Benign	0.59
PhyloP100		-3.1
PromoterAI		0.083	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs4726576; hg19: chr7-142457132; COSMIC: COSV61195680;