5-147828151-T-A

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.88-23A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,561,578 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 8 hom. )

Consequence

SPINK1
NM_001379610.1 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.915

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 5-147828151-T-A is Benign according to our data. Variant chr5-147828151-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 239508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-147828151-T-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00208 (316/152280) while in subpopulation NFE AF = 0.00378 (257/68006). AF 95% confidence interval is 0.0034. There are 0 homozygotes in GnomAd4. There are 140 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 316 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK1	NM_001379610.1 link	c.88-23A>T		intron_variant	Intron 2 of 3	ENST00000296695.10	NP_001366539.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPINK1	ENST00000296695.10 link	c.88-23A>T	intron_variant	Intron 2 of 3	1	NM_001379610.1	ENSP00000296695.5	P00995
SPINK1	ENST00000510027.2 link	c.88-23A>T	intron_variant	Intron 2 of 2	3		ENSP00000427376.1	D6RIU5
SPINK1	ENST00000505722.1 link	n.-21A>T	upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

316

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00378

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00246

AC:

590

AN:

239486

AF XY:

0.00256

show subpopulations

Gnomad AFR exome

AF:

0.000319

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00296

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000935

Gnomad NFE exome

AF:

0.00451

Gnomad OTH exome

AF:

0.00270

GnomAD4 exome

AF:

0.00280

AC:

3945

AN:

1409298

Hom.:

Cov.:

AF XY:

0.00280

AC XY:

1970

AN XY:

703776

show subpopulations

Gnomad4 AFR exome

AF:

0.000432

AC:

AN:

32390

Gnomad4 AMR exome

AF:

0.00104

AC:

AN:

44326

Gnomad4 ASJ exome

AF:

0.00249

AC:

AN:

25712

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39154

Gnomad4 SAS exome

AF:

0.0000592

AC:

AN:

84466

Gnomad4 FIN exome

AF:

0.00135

AC:

AN:

51886

Gnomad4 NFE exome

AF:

0.00339

AC:

3619

AN:

1067126

Gnomad4 Remaining exome

AF:

0.00207

AC:

121

AN:

58568

Heterozygous variant carriers

191

381

572

762

953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

112

224

336

448

560

<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:

0.00208

AC:

316

AN:

152280

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

140

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000337

AC:

0.000336895

AN:

0.000336895

Gnomad4 AMR

AF:

0.00163

AC:

0.00163463

AN:

0.00163463

Gnomad4 ASJ

AF:

0.00173

AC:

0.00172911

AN:

0.00172911

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000207

AC:

0.000207211

AN:

0.000207211

Gnomad4 FIN

AF:

0.000942

AC:

0.00094162

AN:

0.00094162

Gnomad4 NFE

AF:

0.00378

AC:

0.00377908

AN:

0.00377908

Gnomad4 OTH

AF:

0.00142

AC:

0.00141777

AN:

0.00141777

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.00237

Hom.:

Bravo

AF:

0.00202

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

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

- -

Feb 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 26, 2020

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Mar 31, 2020

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:3

May 22, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 24, 2024

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

- -

Hereditary pancreatitis;C1842402:Tropical pancreatitis

Benign:1

May 23, 2022

Fulgent Genetics, Fulgent Genetics

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

-0.80

CADD

Benign

DANN

Benign

0.64

La Branchor

0.60

BranchPoint Hunter

0.0

Mutation Taster

=100/0

polymorphism

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

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