rs79438751

Positions:

• chr5-147831618-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.64

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]

LOC124901101 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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/exons	MANE	UniProt
SPINK1	NM_001379610.1	c.-41G>A		5_prime_UTR_variant	1/4	ENST00000296695.10
LOC124901101	XR_007058987.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINK1	ENST00000296695.10	c.-41G>A		5_prime_UTR_variant	1/4	1	NM_001379610.1	P1
SPINK1	ENST00000510027.2	c.-41G>A		5_prime_UTR_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5502 AN: 152154 Hom.: 322 Cov.: 33

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

GnomAD3 exomes AF: 0.00962 AC: 2375 AN: 246800 Hom.: 155 AF XY: 0.00713 AC XY: 952 AN XY: 133544

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 SAS exome AF: 0.0000660

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.: 30 AF XY: 0.00305 AC XY: 2212 AN XY: 725792

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.00778

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000232

Gnomad4 FIN exome AF: 0.0000382

Gnomad4 NFE exome AF: 0.000261

Gnomad4 OTH exome AF: 0.00812

GnomAD4 genome AF: 0.0362 AC: 5509 AN: 152272 Hom.: 322 Cov.: 33 AF XY: 0.0354 AC XY: 2633 AN XY: 74464

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0210 Hom.: 45

Bravo AF: 0.0425

Asia WGS AF: 0.00953 AC: 33 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary pancreatitis Benign:4

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	curation	Sema4, Sema4	Dec 09, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 24, 2023	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.21
DANN	Benign	0.38

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

LitVar

Other links and lift over

dbSNP: rs79438751; hg19: chr5-147211181;