rs17107318

Variant names:

• chr5-147829667-A-G
• rs17107318
• NM_001379610.1:c.56-37T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign; risk factor criteria provided, multiple submitters, no conflicts B:5 O:1
• Conservation: PhyloP100: -0.216
• Publications: 14 publications found

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

ACMG classification

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 Benign/Likely_benign|risk_factor. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379610.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK1	NM_001379610.1	MANE Select	c.56-37T>C		intron	N/A	NP_001366539.1
	SPINK1	NM_001354966.2		c.56-37T>C		intron	N/A	NP_001341895.1
	SPINK1	NM_003122.5		c.56-37T>C		intron	N/A	NP_003113.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK1	ENST00000296695.10	TSL:1 MANE Select	c.56-37T>C		intron	N/A	ENSP00000296695.5
	SPINK1	ENST00000510027.2	TSL:3	c.56-37T>C		intron	N/A	ENSP00000427376.1

Frequencies

GnomAD3 genomes AF: 0.00761 AC: 1158 AN: 152212 Hom.: 6 Cov.: 33

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

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.: 27 AF XY: 0.0102 AC XY: 7332 AN XY: 716858

African (AFR) AF: 0.00109 AC: 36 AN: 32986

American (AMR) AF: 0.00224 AC: 100 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00112 AC: 29 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: 10 AN: 5722

European-Non Finnish (NFE) AF: 0.0100 AC: 10963 AN: 1091038

Other (OTH) AF: 0.00961 AC: 572 AN: 59546

GnomAD4 genome AF: 0.00760 AC: 1158 AN: 152330 Hom.: 6 Cov.: 33 AF XY: 0.00779 AC XY: 580 AN XY: 74500

African (AFR) AF: 0.00233 AC: 97 AN: 41566

American (AMR) AF: 0.00418 AC: 64 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00541 AC: 28 AN: 5176

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4832

European-Finnish (FIN) AF: 0.0177 AC: 188 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00998 AC: 679 AN: 68034

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00720 Hom.: 1

Bravo AF: 0.00604

Asia WGS AF: 0.0340 AC: 119 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign; risk factor

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hereditary pancreatitis (4)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17107318; hg19: chr5-147209230;