rs17107318

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001379610.1(SPINK1):c.56-37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00971 in 1,590,006 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,risk factor (★★).

Frequency

Genomes: 𝑓 0.0076 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0099 ( 102 hom. )

Consequence

SPINK1
NM_001379610.1 intron

Scores

Clinical Significance

Benign/Likely benign; risk factor criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: -0.216

Variant links:

Genes affected

SPINK1 (HGNC:11244): (serine peptidase inhibitor Kazal type 1) The protein encoded by this gene is a trypsin inhibitor, which is secreted from pancreatic acinar cells into pancreatic juice. It is thought to function in the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Mutations in this gene are associated with hereditary pancreatitis and tropical calcific pancreatitis. [provided by RefSeq, Oct 2008]

SPINK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-147829667-A-G is Benign according to our data. Variant chr5-147829667-A-G is described in ClinVar as [Likely_benign, risk_factor]. Clinvar id is 239507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0076 (1158/152330) while in subpopulation SAS AF= 0.0153 (74/4832). AF 95% confidence interval is 0.0125. There are 6 homozygotes in gnomad4. There are 580 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1158 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK1	NM_001379610.1 link	c.56-37T>C		intron_variant	Intron 1 of 3	ENST00000296695.10	NP_001366539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK1	ENST00000296695.10 link	c.56-37T>C		intron_variant	Intron 1 of 3	1	NM_001379610.1	ENSP00000296695.5		P00995
SPINK1	ENST00000510027.2 link	c.56-37T>C		intron_variant	Intron 1 of 2	3		ENSP00000427376.1		D6RIU5

Frequencies

GnomAD3 genomes

AF:

0.00761

AC:

1158

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.0155

Gnomad FIN

AF:

0.0177

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00998

Gnomad OTH

AF:

0.00955

GnomAD3 exomes

AF:

0.00825

AC:

2055

AN:

249204

Hom.:

AF XY:

0.00898

AC XY:

1210

AN XY:

134712

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.000897

Gnomad EAS exome

AF:

0.00219

Gnomad SAS exome

AF:

0.0171

Gnomad FIN exome

AF:

0.0171

Gnomad NFE exome

AF:

0.00873

Gnomad OTH exome

AF:

0.00724

GnomAD4 exome

AF:

0.00993

AC:

14282

AN:

1437676

Hom.:

102

Cov.:

AF XY:

0.0102

AC XY:

7332

AN XY:

716858

show subpopulations

Gnomad4 AFR exome

AF:

0.00109

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00112

Gnomad4 EAS exome

AF:

0.00410

Gnomad4 SAS exome

AF:

0.0184

Gnomad4 FIN exome

AF:

0.0158

Gnomad4 NFE exome

AF:

0.0100

Gnomad4 OTH exome

AF:

0.00961

GnomAD4 genome

AF:

0.00760

AC:

1158

AN:

152330

Hom.:

Cov.:

AF XY:

0.00779

AC XY:

580

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00541

Gnomad4 SAS

AF:

0.0153

Gnomad4 FIN

AF:

0.0177

Gnomad4 NFE

AF:

0.00998

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00720

Hom.:

Bravo

AF:

0.00604

Asia WGS

AF:

0.0340

AC:

119

AN:

3476

ClinVar

Significance: Benign/Likely benign; risk factor

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary pancreatitis

Benign:3Other:1

Feb 25, 2021

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 08, 2016

Labcorp Genetics (formerly Invitae), Labcorp

Significance: risk factor

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 26, 2023

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. -

not provided

Benign:2

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SPINK1: BS1, BS2 -

Nov 19, 2024

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

-0.90

CADD

Benign

1.4

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over