rs4705204

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr5-147835557-T-C
• chr5-147835557-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001354966.2(SPINK1):​c.-225+3577A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPINK1	NM_001354966.2	c.-225+3577A>G		intron_variant	Intron 1 of 4		NP_001341895.1
SPINK1	NM_003122.5	c.-192+3577A>G		intron_variant	Intron 1 of 4		NP_003113.2
SPINK1	XM_047417625.1	c.-192+1206A>G		intron_variant	Intron 2 of 5		XP_047273581.1
SPINK1	XM_047417626.1	c.-225+1206A>G		intron_variant	Intron 2 of 5		XP_047273582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.89
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;