5-147835557-T-G

Variant names:

• chr5-147835557-T-G
• rs4705204
• NM_001354966.2:c.-225+3577A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354966.2(SPINK1):​c.-225+3577A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,944 control chromosomes in the GnomAD database, including 3,946 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3946 hom., cov: 32)
• Consequence: SPINK1 NM_001354966.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354966.2. 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_001354966.2		c.-225+3577A>C		intron	N/A	NP_001341895.1
	SPINK1	NM_003122.5		c.-192+3577A>C		intron	N/A	NP_003113.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33047 AN: 151826 Hom.: 3944 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.212

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.218 AC: 33088 AN: 151944 Hom.: 3946 Cov.: 32 AF XY: 0.220 AC XY: 16356 AN XY: 74242

African (AFR) AF: 0.212 AC: 8803 AN: 41476

American (AMR) AF: 0.228 AC: 3472 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3466

East Asian (EAS) AF: 0.545 AC: 2802 AN: 5142

South Asian (SAS) AF: 0.310 AC: 1493 AN: 4822

European-Finnish (FIN) AF: 0.182 AC: 1925 AN: 10568

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13108 AN: 67896

Other (OTH) AF: 0.210 AC: 444 AN: 2114

Alfa AF: 0.207 Hom.: 10912

Bravo AF: 0.225

Asia WGS AF: 0.401 AC: 1391 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.049

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4705204; hg19: chr5-147215120; COSMIC: COSV57024389;