rs3809863
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000212.3(ITGB3):c.2301+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,612,228 control chromosomes in the GnomAD database, including 174,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Genomes: 𝑓 0.46 ( 16187 hom., cov: 32)
Exomes 𝑓: 0.46 ( 158722 hom. )
Consequence
ITGB3
NM_000212.3 intron
NM_000212.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.370
Genes affected
ITGB3 (HGNC:6156): (integrin subunit beta 3) The ITGB3 protein product is the integrin beta chain beta 3. Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. A given chain may combine with multiple partners resulting in different integrins. Integrin beta 3 is found along with the alpha IIb chain in platelets. Integrins are known to participate in cell adhesion as well as cell-surface mediated signalling. [provided by RefSeq, Jul 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=-0.83).
BP6
?
Variant 17-47307646-C-T is Benign according to our data. Variant chr17-47307646-C-T is described in ClinVar as [Benign]. Clinvar id is 255539.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr17-47307646-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGB3 | NM_000212.3 | c.2301+9C>T | intron_variant | ENST00000559488.7 | |||
EFCAB13-DT | NR_110880.1 | n.363-3864G>A | intron_variant, non_coding_transcript_variant | ||||
EFCAB13-DT | NR_110881.1 | n.227-3864G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGB3 | ENST00000559488.7 | c.2301+9C>T | intron_variant | 1 | NM_000212.3 | P1 | |||
EFCAB13-DT | ENST00000575039.1 | n.227-3864G>A | intron_variant, non_coding_transcript_variant | 5 | |||||
ITGB3 | ENST00000696963.1 | c.2310C>T | p.Asp770= | synonymous_variant | 14/14 |
Frequencies
GnomAD3 genomes ? AF: 0.456 AC: 69311AN: 151934Hom.: 16185 Cov.: 32
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GnomAD3 exomes AF: 0.429 AC: 107220AN: 249968Hom.: 23739 AF XY: 0.431 AC XY: 58200AN XY: 135070
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GnomAD4 exome AF: 0.463 AC: 676003AN: 1460176Hom.: 158722 Cov.: 36 AF XY: 0.461 AC XY: 335190AN XY: 726390
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GnomAD4 genome ? AF: 0.456 AC: 69347AN: 152052Hom.: 16187 Cov.: 32 AF XY: 0.453 AC XY: 33674AN XY: 74310
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Glanzmann thrombasthenia Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, reviewed by expert panel | curation | ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen | Apr 06, 2023 | After a comprehensive literature search of the intronic variant NM_000212.3(ITGB3):c.2301+9C>T, no individuals with Glanzmann Thrombasthenia were reported with the variant. The variant has a high minor allele frequency of 0.4805 (11916/24800 alleles) in the African/African American population, which is higher than the ClinGen PD VCEP threshold (>0.0024), and therefore meets BA1. In silico predictor spliceAI revealed that the intronic mutation is not expected to impact splicing and a PhyloP score of -.336 shows that the nucleotide position is not highly conserved (BP4,BP7). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4 and BP7 (PD VCEP specifications version 2.1). - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 08, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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