rs758041497
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 4P and 16B. PVS1_StrongBP6_Very_StrongBA1
The NM_000173.7(GP1BA):βc.1305_1320delβ(p.Thr436GlnfsTer31) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (β β ). Synonymous variant affecting the same amino acid position (i.e. T435T) has been classified as Likely benign.
Frequency
Genomes: π 0.31 ( 965 hom., cov: 0)
Exomes π: 0.14 ( 4827 hom. )
Failed GnomAD Quality Control
Consequence
GP1BA
NM_000173.7 frameshift
NM_000173.7 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.945
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 -12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 6 pathogenic variants in the truncated region.
BP6
Variant 17-4933907-ACCACCCCAGAGCCCAC-A is Benign according to our data. Variant chr17-4933907-ACCACCCCAGAGCCCAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 435345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GP1BA | NM_000173.7 | c.1305_1320del | p.Thr436GlnfsTer31 | frameshift_variant | 2/2 | ENST00000329125.6 | NP_000164.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GP1BA | ENST00000329125.6 | c.1305_1320del | p.Thr436GlnfsTer31 | frameshift_variant | 2/2 | 1 | NM_000173.7 | ENSP00000329380 | P1 | |
CHRNE | ENST00000649830.1 | c.-888+419_-888+434del | intron_variant | ENSP00000496907 |
Frequencies
GnomAD3 genomes AF: 0.308 AC: 10508AN: 34096Hom.: 965 Cov.: 0
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GnomAD3 exomes AF: 0.0706 AC: 9463AN: 133946Hom.: 909 AF XY: 0.0679 AC XY: 4952AN XY: 72910
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.138 AC: 61162AN: 443146Hom.: 4827 AF XY: 0.152 AC XY: 34213AN XY: 225518
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GnomAD4 genome AF: 0.308 AC: 10511AN: 34110Hom.: 965 Cov.: 0 AF XY: 0.303 AC XY: 4924AN XY: 16272
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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 provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 06, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 16, 2016 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at