5-147829667-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

hereditary chronic pancreatitis
Inheritance: AD, Unknown Classification: STRONG, SUPPORTIVE, NO_KNOWN Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia
tropical pancreatitis
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

SPINK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1158 AD,Unknown 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

GnomAD2 exomes

AF:

0.00825

AC:

2055

AN:

249204

AF XY:

0.00898

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 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

African (AFR)

AF:

0.00109

AC:

AN:

32986

American (AMR)

AF:

0.00224

AC:

100

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00112

AC:

AN:

25988

East Asian (EAS)

AF:

0.00410

AC:

162

AN:

39486

South Asian (SAS)

AF:

0.0184

AC:

1579

AN:

85702

European-Finnish (FIN)

AF:

0.0158

AC:

831

AN:

52564

Middle Eastern (MID)

AF:

0.00175

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.0100

AC:

10963

AN:

1091038

Other (OTH)

AF:

0.00961

AC:

572

AN:

59546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

646

1292

1938

2584

3230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

442

884

1326

1768

2210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00760

AC:

1158

AN:

152330

Hom.:

Cov.:

AF XY:

0.00779

AC XY:

580

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

41566

American (AMR)

AF:

0.00418

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00541

AC:

AN:

5176

South Asian (SAS)

AF:

0.0153

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0177

AC:

188

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00998

AC:

679

AN:

68034

Other (OTH)

AF:

0.0104

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

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. -

Feb 25, 2021

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Mar 08, 2016

Labcorp Genetics (formerly Invitae), Labcorp

Significance:risk factor

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 19, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SPINK1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.58

PhyloP100

-0.22

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over