5-147827838-A-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001379610.1(SPINK1):c.194+184T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 526,370 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 12 hom., cov: 32)
Exomes 𝑓: 0.013 ( 57 hom. )
Consequence
SPINK1
NM_001379610.1 intron
NM_001379610.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.225
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 5-147827838-A-T is Benign according to our data. Variant chr5-147827838-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 239506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0104 (1588/152286) while in subpopulation NFE AF= 0.0172 (1172/68016). AF 95% confidence interval is 0.0164. There are 12 homozygotes in gnomad4. There are 706 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1588 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPINK1 | NM_001379610.1 | c.194+184T>A | intron_variant | ENST00000296695.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPINK1 | ENST00000296695.10 | c.194+184T>A | intron_variant | 1 | NM_001379610.1 | P1 | |||
SPINK1 | ENST00000510027.2 | c.*180T>A | 3_prime_UTR_variant | 3/3 | 3 | ||||
SPINK1 | ENST00000505722.1 | n.109+184T>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0104 AC: 1587AN: 152168Hom.: 12 Cov.: 32
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GnomAD4 exome AF: 0.0130 AC: 4863AN: 374084Hom.: 57 Cov.: 4 AF XY: 0.0127 AC XY: 2519AN XY: 197978
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GnomAD4 genome AF: 0.0104 AC: 1588AN: 152286Hom.: 12 Cov.: 32 AF XY: 0.00948 AC XY: 706AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary pancreatitis Benign:3
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 05, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 06, 2018 | This variant is associated with the following publications: (PMID: 10982753, 28472998) - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at