5-147831618-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001379610.1(SPINK1):c.-41G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00658 in 1,611,154 control chromosomes in the GnomAD database, including 579 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 322 hom., cov: 33)

Exomes 𝑓: 0.0035 ( 257 hom. )

Consequence

SPINK1
NM_001379610.1 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.64

Publications

5 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:

LOC124901101 (HGNC:):

LOC124901101 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=-0.89).

BP6

Variant 5-147831618-C-T is Benign according to our data. Variant chr5-147831618-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK1	NM_001379610.1 link	c.-41G>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000296695.10	NP_001366539.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPINK1	ENST00000296695.10 link	c.-41G>A		5_prime_UTR_variant	Exon 1 of 4	1	NM_001379610.1	ENSP00000296695.5		P00995
SPINK1	ENST00000510027.2 link	c.-41G>A		5_prime_UTR_variant	Exon 1 of 3	3		ENSP00000427376.1		D6RIU5

Frequencies

GnomAD3 genomes

AF:

0.0362

AC:

5502

AN:

152154

Hom.:

322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.00962

AC:

2375

AN:

246800

AF XY:

0.00713

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.00673

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000489

Gnomad NFE exome

AF:

0.000287

Gnomad OTH exome

AF:

0.00595

GnomAD4 exome

AF:

0.00349

AC:

5085

AN:

1458882

Hom.:

257

Cov.:

AF XY:

0.00305

AC XY:

2212

AN XY:

725792

show subpopulations

African (AFR)

AF:

0.117

AC:

3910

AN:

33364

American (AMR)

AF:

0.00778

AC:

347

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39426

South Asian (SAS)

AF:

0.000232

AC:

AN:

86052

European-Finnish (FIN)

AF:

0.0000382

AC:

AN:

52324

Middle Eastern (MID)

AF:

0.00452

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.000261

AC:

290

AN:

1111010

Other (OTH)

AF:

0.00812

AC:

489

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

265

530

794

1059

1324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<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:

0.0362

AC:

5509

AN:

152272

Hom.:

322

Cov.:

AF XY:

0.0354

AC XY:

2633

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.125

AC:

5198

AN:

41540

American (AMR)

AF:

0.0144

AC:

220

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68034

Other (OTH)

AF:

0.0255

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

243

487

730

974

1217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0210

Hom.:

Bravo

AF:

0.0425

Asia WGS

AF:

0.00953

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary pancreatitis

Benign:4

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 08, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Dec 09, 2019

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 22, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27884173, 17003641, 21610753) -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.89

CADD

Benign

0.21

(source)

DANN

Benign

0.38

PhyloP100

-2.6

PromoterAI

-0.032

Neutral

(source)

Mutation Taster

=297/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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