rs79438751

Variant names:

• chr5-147831618-C-T
• rs79438751
• NM_001379610.1:c.-41G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-147831618-C-T
• chr5-147831618-C-A

Variant summary

Our verdict is Benign. The variant received -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:7
• Conservation: PhyloP100: -2.64
• Publications: 5 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

LOC124901101 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

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.-41G>A		5_prime_UTR	Exon 1 of 4	NP_001366539.1	P00995
	SPINK1	NM_001354966.2		c.-41G>A		5_prime_UTR	Exon 2 of 5	NP_001341895.1	P00995
	SPINK1	NM_003122.5		c.-41G>A		5_prime_UTR	Exon 2 of 5	NP_003113.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPINK1	ENST00000296695.10	TSL:1 MANE Select	c.-41G>A		5_prime_UTR	Exon 1 of 4	ENSP00000296695.5	P00995
	SPINK1	ENST00000510027.2	TSL:3	c.-41G>A		5_prime_UTR	Exon 1 of 3	ENSP00000427376.1	D6RIU5

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

GnomAD2 exomes AF: 0.00962 AC: 2375 AN: 246800 AF XY: 0.00713

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 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

African (AFR) AF: 0.117 AC: 3910 AN: 33364

American (AMR) AF: 0.00778 AC: 347 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39426

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86052

European-Finnish (FIN) AF: 0.0000382 AC: 2 AN: 52324

Middle Eastern (MID) AF: 0.00452 AC: 26 AN: 5748

European-Non Finnish (NFE) AF: 0.000261 AC: 290 AN: 1111010

Other (OTH) AF: 0.00812 AC: 489 AN: 60258

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

African (AFR) AF: 0.125 AC: 5198 AN: 41540

American (AMR) AF: 0.0144 AC: 220 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68034

Other (OTH) AF: 0.0255 AC: 54 AN: 2114

Alfa AF: 0.0210 Hom.: 45

Bravo AF: 0.0425

Asia WGS AF: 0.00953 AC: 33 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Hereditary pancreatitis (4)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.21
DANN	Benign	0.38
PhyloP100		-2.6
PromoterAI		-0.032	Neutral
Mutation Taster		=297/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79438751; hg19: chr5-147211181;