rs114094661

Variant names:

• chr5-147827838-A-T
• rs114094661
• NM_001379610.1:c.194+184T>A

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.194+184T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 526,370 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (12 hom., cov: 32)
  • Exomes 𝑓: 0.013 (57 hom.)
• Consequence: SPINK1 NM_001379610.1 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.225
• Publications: 4 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, MODERATE, SUPPORTIVE, NO_KNOWN Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-147827838-A-T is Benign according to our data. Variant chr5-147827838-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 239506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0104 (1588/152286) while in subpopulation NFE AF = 0.0172 (1172/68016). AF 95% confidence interval is 0.0164. There are 12 homozygotes in GnomAd4. There are 706 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1588 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK1	NM_001379610.1	MANE Select	c.194+184T>A		intron	N/A	NP_001366539.1	P00995
	SPINK1	NM_001354966.2		c.194+184T>A		intron	N/A	NP_001341895.1	P00995
	SPINK1	NM_003122.5		c.194+184T>A		intron	N/A	NP_003113.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK1	ENST00000296695.10	TSL:1 MANE Select	c.194+184T>A		intron	N/A	ENSP00000296695.5	P00995
	SPINK1	ENST00000510027.2	TSL:3	c.*180T>A		3_prime_UTR	Exon 3 of 3	ENSP00000427376.1	D6RIU5
	SPINK1	ENST00000505722.1	TSL:2	n.109+184T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1587 AN: 152168 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.0130 AC: 4863 AN: 374084 Hom.: 57 Cov.: 4 AF XY: 0.0127 AC XY: 2519 AN XY: 197978

African (AFR) AF: 0.00376 AC: 41 AN: 10896

American (AMR) AF: 0.00658 AC: 93 AN: 14138

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 129 AN: 11560

East Asian (EAS) AF: 0.00 AC: 0 AN: 26544

South Asian (SAS) AF: 0.00476 AC: 156 AN: 32758

European-Finnish (FIN) AF: 0.00661 AC: 148 AN: 22382

Middle Eastern (MID) AF: 0.00122 AC: 2 AN: 1640

European-Non Finnish (NFE) AF: 0.0172 AC: 3991 AN: 232218

Other (OTH) AF: 0.0138 AC: 303 AN: 21948

GnomAD4 genome AF: 0.0104 AC: 1588 AN: 152286 Hom.: 12 Cov.: 32 AF XY: 0.00948 AC XY: 706 AN XY: 74472

African (AFR) AF: 0.00291 AC: 121 AN: 41568

American (AMR) AF: 0.00588 AC: 90 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4826

European-Finnish (FIN) AF: 0.00499 AC: 53 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0172 AC: 1172 AN: 68016

Other (OTH) AF: 0.0137 AC: 29 AN: 2110

Alfa AF: 0.0156 Hom.: 4

Bravo AF: 0.00971

Asia WGS AF: 0.000290 AC: 1 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hereditary pancreatitis (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.65
PhyloP100		-0.23
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

Other links and lift over

dbSNP: rs114094661; hg19: chr5-147207401;