5-147824610-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001379610.1(SPINK1):c.*51T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,563,590 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0098 (16 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (29 hom.)
• Consequence: SPINK1 NM_001379610.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.278

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-147824610-A-G is Benign according to our data. Variant chr5-147824610-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 351508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00981 (1494/152316) while in subpopulation AFR AF= 0.032 (1332/41570). AF 95% confidence interval is 0.0306. There are 16 homozygotes in gnomad4. There are 724 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1487 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPINK1	NM_001379610.1	c.*51T>C		3_prime_UTR_variant	4/4	ENST00000296695.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPINK1	ENST00000296695.10	c.*51T>C		3_prime_UTR_variant	4/4	1	NM_001379610.1	P1
SPINK1	ENST00000505722.1	n.206T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.00977 AC: 1487 AN: 152198 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00727

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: 0.000382

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00258 AC: 645 AN: 249940 Hom.: 10 AF XY: 0.00185 AC XY: 250 AN XY: 135102

Gnomad AFR exome AF: 0.0322

Gnomad AMR exome AF: 0.00247

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000275

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00115 AC: 1626 AN: 1411274 Hom.: 29 Cov.: 25 AF XY: 0.00103 AC XY: 729 AN XY: 705174

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.00260

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000471

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000228

Gnomad4 OTH exome AF: 0.00238

GnomAD4 genome AF: 0.00981 AC: 1494 AN: 152316 Hom.: 16 Cov.: 33 AF XY: 0.00972 AC XY: 724 AN XY: 74478

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.00726

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00380 Hom.: 4

Bravo AF: 0.0110

Asia WGS AF: 0.00202 AC: 7 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary pancreatitis Benign:1

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). No publications were found based on this search. Allele frequency data from public databases allowed determination 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	-0.85
Cadd	Benign	3.3
Dann	Benign	0.50

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

Other links and lift over

dbSNP: rs113527737; hg19: chr5-147204173; COSMIC: COSV57024840; COSMIC: COSV57024840;