rs6667

Variant names:

• chr7-142753014-T-C
• rs6667
• NM_002769.5:c.738T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-142753014-T-C
• chr7-142753014-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002769.5(PRSS1):​c.738T>C​(p.Asn246Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,609,686 control chromosomes in the GnomAD database, including 244,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21021 hom., cov: 26)
  • Exomes 𝑓: 0.55 (223124 hom.)
• Consequence: PRSS1 NM_002769.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.244
• Publications: 28 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: Illumina, ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• malignant pancreatic neoplasm

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

TRB (HGNC:12155):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 7-142753014-T-C is Benign according to our data. Variant chr7-142753014-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.244 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	NM_002769.5	MANE Select	c.738T>C	p.Asn246Asn	synonymous	Exon 5 of 5	NP_002760.1	P07477
	PRSS1	NR_172947.1		n.680T>C		non_coding_transcript_exon	Exon 5 of 5
	PRSS1	NR_172948.1		n.677T>C		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS1	ENST00000311737.12	TSL:1 MANE Select	c.738T>C	p.Asn246Asn	synonymous	Exon 5 of 5	ENSP00000308720.7	P07477
	PRSS1	ENST00000486171.5	TSL:5	c.780T>C	p.Asn260Asn	synonymous	Exon 6 of 6	ENSP00000417854.1	E7EQ64
	PRSS1	ENST00000492062.2	TSL:2	c.*142T>C		3_prime_UTR	Exon 5 of 5	ENSP00000419912.2	H0Y8D1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 78354 AN: 148648 Hom.: 21011 Cov.: 26

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.536

GnomAD2 exomes AF: 0.508 AC: 127743 AN: 251370 AF XY: 0.502

Gnomad AFR exome AF: 0.432

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.562

Gnomad EAS exome AF: 0.229

Gnomad FIN exome AF: 0.606

Gnomad NFE exome AF: 0.578

Gnomad OTH exome AF: 0.531

GnomAD4 exome AF: 0.546 AC: 797113 AN: 1460926 Hom.: 223124 Cov.: 51 AF XY: 0.539 AC XY: 391917 AN XY: 726840

African (AFR) AF: 0.431 AC: 14393 AN: 33390

American (AMR) AF: 0.567 AC: 25344 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 14673 AN: 26126

East Asian (EAS) AF: 0.248 AC: 9862 AN: 39694

South Asian (SAS) AF: 0.315 AC: 27127 AN: 86240

European-Finnish (FIN) AF: 0.601 AC: 32106 AN: 53416

Middle Eastern (MID) AF: 0.437 AC: 2520 AN: 5762

European-Non Finnish (NFE) AF: 0.576 AC: 640358 AN: 1111208

Other (OTH) AF: 0.509 AC: 30730 AN: 60374

GnomAD4 genome AF: 0.527 AC: 78405 AN: 148760 Hom.: 21021 Cov.: 26 AF XY: 0.523 AC XY: 38000 AN XY: 72726

African (AFR) AF: 0.464 AC: 18031 AN: 38880

American (AMR) AF: 0.575 AC: 8666 AN: 15072

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1993 AN: 3460

East Asian (EAS) AF: 0.225 AC: 1149 AN: 5102

South Asian (SAS) AF: 0.309 AC: 1463 AN: 4732

European-Finnish (FIN) AF: 0.602 AC: 6302 AN: 10466

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39097 AN: 67776

Other (OTH) AF: 0.532 AC: 1105 AN: 2078

Alfa AF: 0.543 Hom.: 15043

Bravo AF: 0.518

Asia WGS AF: 0.273 AC: 955 AN: 3478

EpiCase AF: 0.566

EpiControl AF: 0.577

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Hereditary pancreatitis (5)
-	-	5	not specified (5)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.0
DANN	Benign	0.30
PhyloP100		0.24
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs6667; hg19: chr7-142460865; COSMIC: COSV61193305; COSMIC: COSV61193305;