rs869060239
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1
The NM_000173.7(GP1BA):c.1282_1359delTCAGAGCCCGCCCCCAGCCCGACCACCCCAGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCCGGAGCCCACC(p.Ser428_Thr453del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 144,606 control chromosomes in the GnomAD database, including 72 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.017 ( 72 hom., cov: 26)
Exomes 𝑓: 0.026 ( 1927 hom. )
Failed GnomAD Quality Control
Consequence
GP1BA
NM_000173.7 conservative_inframe_deletion
NM_000173.7 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.807
Genes affected
GP1BA (HGNC:4439): (glycoprotein Ib platelet subunit alpha) Glycoprotein Ib (GP Ib) is a platelet surface membrane glycoprotein composed of a heterodimer, an alpha chain and a beta chain, that is linked by disulfide bonds. The Gp Ib functions as a receptor for von Willebrand factor (VWF). The complete receptor complex includes noncovalent association of the alpha and beta subunits with platelet glycoprotein IX and platelet glycoprotein V. The binding of the GP Ib-IX-V complex to VWF facilitates initial platelet adhesion to vascular subendothelium after vascular injury, and also initiates signaling events within the platelet that lead to enhanced platelet activation, thrombosis, and hemostasis. This gene encodes the alpha subunit. Mutations in this gene result in Bernard-Soulier syndromes and platelet-type von Willebrand disease. The coding region of this gene is known to contain a polymophic variable number tandem repeat (VNTR) domain that is associated with susceptibility to nonarteritic anterior ischemic optic neuropathy. [provided by RefSeq, Oct 2013]
CHRNE (HGNC:1966): (cholinergic receptor nicotinic epsilon subunit) Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_000173.7.
BP6
Variant 17-4933822-AAGCCCGACCACCCCAGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCCGGAGCCCACCTCAGAGCCCGCCCCC-A is Benign according to our data. Variant chr17-4933822-AAGCCCGACCACCCCAGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCCGGAGCCCACCTCAGAGCCCGCCCCC-A is described in ClinVar as [Likely_benign]. Clinvar id is 435348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-4933822-AAGCCCGACCACCCCAGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCCGGAGCCCACCTCAGAGCCCGCCCCC-A is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GP1BA | NM_000173.7 | c.1282_1359delTCAGAGCCCGCCCCCAGCCCGACCACCCCAGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCCGGAGCCCACC | p.Ser428_Thr453del | conservative_inframe_deletion | 2/2 | ENST00000329125.6 | NP_000164.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GP1BA | ENST00000329125.6 | c.1282_1359delTCAGAGCCCGCCCCCAGCCCGACCACCCCAGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCCGGAGCCCACC | p.Ser428_Thr453del | conservative_inframe_deletion | 2/2 | 1 | NM_000173.7 | ENSP00000329380.5 | ||
CHRNE | ENST00000649830.1 | c.-888+442_-888+519delGGGGGCGGGCTCTGAGGTGGGCTCCGGGGTGGTCGGGCTGGGGGCGGGCTCTGAGGTGGGCTCTGGGGTGGTCGGGCT | intron_variant | ENSP00000496907.1 |
Frequencies
GnomAD3 genomes AF: 0.0169 AC: 2436AN: 144494Hom.: 72 Cov.: 26
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GnomAD3 exomes AF: 0.0189 AC: 4641AN: 246204Hom.: 219 AF XY: 0.0183 AC XY: 2447AN XY: 133754
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0260 AC: 37517AN: 1443704Hom.: 1927 AF XY: 0.0279 AC XY: 20045AN XY: 717738
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.0168 AC: 2435AN: 144606Hom.: 72 Cov.: 26 AF XY: 0.0164 AC XY: 1150AN XY: 70250
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 26, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Bernard Soulier syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at