chr4-67558935-T-C
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_012108.4(STAP1):c.120+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 1,596,444 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0037 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0046 ( 19 hom. )
Consequence
STAP1
NM_012108.4 splice_donor_region, intron
NM_012108.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.03046
2
Clinical Significance
Conservation
PhyloP100: 0.339
Genes affected
STAP1 (HGNC:24133): (signal transducing adaptor family member 1) The protein encoded by this gene contains a proline-rich region, a pleckstrin homology (PH) domain, and a region in the carboxy terminal half with similarity to the Src Homology 2 (SH2) domain. This protein is a substrate of tyrosine-protein kinase Tec, and its interaction with tyrosine-protein kinase Tec is phosphorylation-dependent. This protein is thought to participate in a positive feedback loop by upregulating the activity of tyrosine-protein kinase Tec. Variants of this gene have been associated with autosomal-dominant hypercholesterolemia (ADH), which is characterized by elevated low-density lipoprotein cholesterol levels and in increased risk of coronary vascular disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 4-67558935-T-C is Benign according to our data. Variant chr4-67558935-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1221906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-67558935-T-C is described in Lovd as [Benign].
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STAP1 | NM_012108.4 | c.120+6T>C | splice_donor_region_variant, intron_variant | ENST00000265404.7 | |||
STAP1 | NM_001317769.2 | c.120+6T>C | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STAP1 | ENST00000265404.7 | c.120+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_012108.4 | P1 | |||
STAP1 | ENST00000396225.1 | c.120+6T>C | splice_donor_region_variant, intron_variant | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00368 AC: 559AN: 152082Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00448 AC: 1070AN: 238888Hom.: 4 AF XY: 0.00460 AC XY: 595AN XY: 129300
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GnomAD4 exome AF: 0.00462 AC: 6677AN: 1444246Hom.: 19 Cov.: 30 AF XY: 0.00463 AC XY: 3327AN XY: 718126
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GnomAD4 genome AF: 0.00367 AC: 559AN: 152198Hom.: 2 Cov.: 32 AF XY: 0.00355 AC XY: 264AN XY: 74388
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 07, 2020 | - - |
STAP1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 01, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -6
Find out detailed SpliceAI scores and Pangolin per-transcript scores at