chr5-147824629-G-A

Variant names:

• chr5-147824629-G-A
• rs11319
• NM_001379610.1:c.*32C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003122.5(SPINK1):​c.*32C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 1,607,666 control chromosomes in the GnomAD database, including 3,805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (382 hom., cov: 32)
  • Exomes 𝑓: 0.050 (3423 hom.)
• Consequence: SPINK1 NM_003122.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0630
• Publications: 20 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=-0.87).
• BP6: Variant 5-147824629-G-A is Benign according to our data. Variant chr5-147824629-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 351510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003122.5. 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.*32C>T		3_prime_UTR	Exon 4 of 4	NP_001366539.1
	SPINK1	NM_001354966.2		c.*32C>T		3_prime_UTR	Exon 5 of 5	NP_001341895.1
	SPINK1	NM_003122.5		c.*32C>T		3_prime_UTR	Exon 5 of 5	NP_003113.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK1	ENST00000296695.10	TSL:1 MANE Select	c.*32C>T		3_prime_UTR	Exon 4 of 4	ENSP00000296695.5
	SPINK1	ENST00000505722.1	TSL:2	n.187C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7926 AN: 152054 Hom.: 382 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0378

Gnomad OTH AF: 0.0493

GnomAD2 exomes AF: 0.0831 AC: 20816 AN: 250526 AF XY: 0.0809

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.0789

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.0381

Gnomad OTH exome AF: 0.0717

GnomAD4 exome AF: 0.0498 AC: 72492 AN: 1455494 Hom.: 3423 Cov.: 30 AF XY: 0.0522 AC XY: 37784 AN XY: 724478

African (AFR) AF: 0.0155 AC: 516 AN: 33328

American (AMR) AF: 0.203 AC: 9073 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.0333 AC: 870 AN: 26100

East Asian (EAS) AF: 0.0799 AC: 3166 AN: 39644

South Asian (SAS) AF: 0.153 AC: 13210 AN: 86086

European-Finnish (FIN) AF: 0.100 AC: 5334 AN: 53362

Middle Eastern (MID) AF: 0.0325 AC: 187 AN: 5758

European-Non Finnish (NFE) AF: 0.0335 AC: 37106 AN: 1106374

Other (OTH) AF: 0.0504 AC: 3030 AN: 60176

GnomAD4 genome AF: 0.0521 AC: 7933 AN: 152172 Hom.: 382 Cov.: 32 AF XY: 0.0597 AC XY: 4439 AN XY: 74384

African (AFR) AF: 0.0187 AC: 775 AN: 41524

American (AMR) AF: 0.136 AC: 2076 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 114 AN: 3468

East Asian (EAS) AF: 0.0846 AC: 437 AN: 5168

South Asian (SAS) AF: 0.158 AC: 759 AN: 4812

European-Finnish (FIN) AF: 0.103 AC: 1093 AN: 10582

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0377 AC: 2567 AN: 68016

Other (OTH) AF: 0.0488 AC: 103 AN: 2112

Alfa AF: 0.0417 Hom.: 583

Bravo AF: 0.0510

Asia WGS AF: 0.106 AC: 369 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.57
PhyloP100		-0.063
Mutation Taster		=100/0	polymorphism (auto)

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: rs11319; hg19: chr5-147204192; COSMIC: COSV57024323; COSMIC: COSV57024323;