rs11319

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.*32C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 1,607,666 control chromosomes in the GnomAD database, including 3,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 382 hom., cov: 32)

Exomes 𝑓: 0.050 ( 3423 hom. )

Consequence

SPINK1
NM_001379610.1 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0630

Publications

20 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=-0.87).

BP6

Variant 5-147824629-G-A is Benign according to our data. Variant chr5-147824629-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 351510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK1	NM_001379610.1 link	c.*32C>T		3_prime_UTR_variant	Exon 4 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.*32C>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_001379610.1	ENSP00000296695.5		P00995
SPINK1	ENST00000505722.1 link	n.187C>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0521

AC:

7926

AN:

152054

Hom.:

382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.0329

Gnomad EAS

AF:

0.0847

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0378

Gnomad OTH

AF:

0.0493

GnomAD2 exomes

AF:

0.0831

AC:

20816

AN:

250526

AF XY:

0.0809

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.0282

Gnomad EAS exome

AF:

0.0789

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0381

Gnomad OTH exome

AF:

0.0717

GnomAD4 exome

AF:

0.0498

AC:

72492

AN:

1455494

Hom.:

3423

Cov.:

AF XY:

0.0522

AC XY:

37784

AN XY:

724478

show subpopulations

African (AFR)

AF:

0.0155

AC:

516

AN:

33328

American (AMR)

AF:

0.203

AC:

9073

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.0333

AC:

870

AN:

26100

East Asian (EAS)

AF:

0.0799

AC:

3166

AN:

39644

South Asian (SAS)

AF:

0.153

AC:

13210

AN:

86086

European-Finnish (FIN)

AF:

0.100

AC:

5334

AN:

53362

Middle Eastern (MID)

AF:

0.0325

AC:

187

AN:

5758

European-Non Finnish (NFE)

AF:

0.0335

AC:

37106

AN:

1106374

Other (OTH)

AF:

0.0504

AC:

3030

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

2948

5896

8845

11793

14741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1552

3104

4656

6208

7760

<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:

0.0521

AC:

7933

AN:

152172

Hom.:

382

Cov.:

AF XY:

0.0597

AC XY:

4439

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0187

AC:

775

AN:

41524

American (AMR)

AF:

0.136

AC:

2076

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0329

AC:

114

AN:

3468

East Asian (EAS)

AF:

0.0846

AC:

437

AN:

5168

South Asian (SAS)

AF:

0.158

AC:

759

AN:

4812

European-Finnish (FIN)

AF:

0.103

AC:

1093

AN:

10582

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0377

AC:

2567

AN:

68016

Other (OTH)

AF:

0.0488

AC:

103

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

361

721

1082

1442

1803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0417

Hom.:

583

Bravo

AF:

0.0510

Asia WGS

AF:

0.106

AC:

369

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 20, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 21, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary pancreatitis

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.6

(source)

DANN

Benign

0.57

PhyloP100

-0.063

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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