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

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.807
Variant links:
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
GP1BANM_000173.7 linkuse as main transcriptc.1282_1359delTCAGAGCCCGCCCCCAGCCCGACCACCCCAGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCCGGAGCCCACC p.Ser428_Thr453del conservative_inframe_deletion 2/2 ENST00000329125.6 NP_000164.5 P07359L7UYB8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GP1BAENST00000329125.6 linkuse as main transcriptc.1282_1359delTCAGAGCCCGCCCCCAGCCCGACCACCCCAGAGCCCACCTCAGAGCCCGCCCCCAGCCCGACCACCCCGGAGCCCACC p.Ser428_Thr453del conservative_inframe_deletion 2/21 NM_000173.7 ENSP00000329380.5 P07359
CHRNEENST00000649830.1 linkuse as main transcriptc.-888+442_-888+519delGGGGGCGGGCTCTGAGGTGGGCTCCGGGGTGGTCGGGCTGGGGGCGGGCTCTGAGGTGGGCTCTGGGGTGGTCGGGCT intron_variant ENSP00000496907.1 A0A3B3IRM1

Frequencies

GnomAD3 genomes
AF:
0.0169
AC:
2436
AN:
144494
Hom.:
72
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.00899
Gnomad AMI
AF:
0.00335
Gnomad AMR
AF:
0.0137
Gnomad ASJ
AF:
0.0375
Gnomad EAS
AF:
0.0630
Gnomad SAS
AF:
0.0321
Gnomad FIN
AF:
0.0237
Gnomad MID
AF:
0.0353
Gnomad NFE
AF:
0.0162
Gnomad OTH
AF:
0.0126
GnomAD3 exomes
AF:
0.0189
AC:
4641
AN:
246204
Hom.:
219
AF XY:
0.0183
AC XY:
2447
AN XY:
133754
show subpopulations
Gnomad AFR exome
AF:
0.00921
Gnomad AMR exome
AF:
0.0146
Gnomad ASJ exome
AF:
0.0187
Gnomad EAS exome
AF:
0.0986
Gnomad SAS exome
AF:
0.0292
Gnomad FIN exome
AF:
0.00510
Gnomad NFE exome
AF:
0.00843
Gnomad OTH exome
AF:
0.0228
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0260
AC:
37517
AN:
1443704
Hom.:
1927
AF XY:
0.0279
AC XY:
20045
AN XY:
717738
show subpopulations
Gnomad4 AFR exome
AF:
0.0123
Gnomad4 AMR exome
AF:
0.0194
Gnomad4 ASJ exome
AF:
0.0610
Gnomad4 EAS exome
AF:
0.216
Gnomad4 SAS exome
AF:
0.0531
Gnomad4 FIN exome
AF:
0.0572
Gnomad4 NFE exome
AF:
0.0152
Gnomad4 OTH exome
AF:
0.0336
GnomAD4 genome
AF:
0.0168
AC:
2435
AN:
144606
Hom.:
72
Cov.:
26
AF XY:
0.0164
AC XY:
1150
AN XY:
70250
show subpopulations
Gnomad4 AFR
AF:
0.00896
Gnomad4 AMR
AF:
0.0136
Gnomad4 ASJ
AF:
0.0375
Gnomad4 EAS
AF:
0.0640
Gnomad4 SAS
AF:
0.0312
Gnomad4 FIN
AF:
0.0237
Gnomad4 NFE
AF:
0.0162
Gnomad4 OTH
AF:
0.0124
Alfa
AF:
0.00380
Hom.:
0

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 submitterclinical testingGenetic Services Laboratory, University of ChicagoOct 26, 2016- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -
Bernard Soulier syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingMendelicsMay 28, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs869060239; hg19: chr17-4837117; API