chr17-47287174-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP7BP4BA1

This summary comes from the ClinGen Evidence Repository: After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.882T>C (p.Pro294=), no individuals with Glanzmann thrombasthenia were reported with the variant. Moreover, the variant has a minor allele frequency of 0.2463 (4912/19940 alleles) in gnomAD, found in the East Asian population, which is considerably higher than the expected frequency of the disease (BA1). In Silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing at a nucleotide site that is not highly conserved. In conclusion the criteria BA1, BP4, and BP7 were applied to reach a classification of benign. LINK:https://erepo.genome.network/evrepo/ui/classification/CA8623073/MONDO:0100326/011

Frequency

Genomes: 𝑓 0.11 ( 1018 hom., cov: 32)
Exomes 𝑓: 0.080 ( 6043 hom. )

Consequence

ITGB3
NM_000212.3 synonymous

Scores

2

Clinical Significance

Benign reviewed by expert panel B:6

Conservation

PhyloP100: 1.03
Variant links:
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 -10 ACMG points.

BP4
For more information check the summary or visit ClinGen Evidence Repository.
BP7
For more information check the summary or visit ClinGen Evidence Repository.
BA1
For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ITGB3NM_000212.3 linkuse as main transcriptc.882T>C p.Pro294= synonymous_variant 6/15 ENST00000559488.7 NP_000203.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ITGB3ENST00000559488.7 linkuse as main transcriptc.882T>C p.Pro294= synonymous_variant 6/151 NM_000212.3 ENSP00000452786 P1P05106-1
ITGB3ENST00000571680.1 linkuse as main transcriptc.882T>C p.Pro294= synonymous_variant 6/91 ENSP00000461626
ITGB3ENST00000696963.1 linkuse as main transcriptc.882T>C p.Pro294= synonymous_variant 6/14 ENSP00000513002 P05106-2

Frequencies

GnomAD3 genomes
AF:
0.105
AC:
15995
AN:
152084
Hom.:
1009
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.157
Gnomad AMI
AF:
0.146
Gnomad AMR
AF:
0.0880
Gnomad ASJ
AF:
0.147
Gnomad EAS
AF:
0.240
Gnomad SAS
AF:
0.167
Gnomad FIN
AF:
0.0352
Gnomad MID
AF:
0.171
Gnomad NFE
AF:
0.0708
Gnomad OTH
AF:
0.112
GnomAD3 exomes
AF:
0.100
AC:
25242
AN:
251236
Hom.:
1723
AF XY:
0.103
AC XY:
13938
AN XY:
135784
show subpopulations
Gnomad AFR exome
AF:
0.159
Gnomad AMR exome
AF:
0.0567
Gnomad ASJ exome
AF:
0.141
Gnomad EAS exome
AF:
0.245
Gnomad SAS exome
AF:
0.158
Gnomad FIN exome
AF:
0.0393
Gnomad NFE exome
AF:
0.0746
Gnomad OTH exome
AF:
0.103
GnomAD4 exome
AF:
0.0802
AC:
117232
AN:
1461626
Hom.:
6043
Cov.:
33
AF XY:
0.0827
AC XY:
60153
AN XY:
727118
show subpopulations
Gnomad4 AFR exome
AF:
0.157
Gnomad4 AMR exome
AF:
0.0613
Gnomad4 ASJ exome
AF:
0.138
Gnomad4 EAS exome
AF:
0.221
Gnomad4 SAS exome
AF:
0.160
Gnomad4 FIN exome
AF:
0.0416
Gnomad4 NFE exome
AF:
0.0664
Gnomad4 OTH exome
AF:
0.0996
GnomAD4 genome
AF:
0.105
AC:
16029
AN:
152202
Hom.:
1018
Cov.:
32
AF XY:
0.105
AC XY:
7815
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.157
Gnomad4 AMR
AF:
0.0879
Gnomad4 ASJ
AF:
0.147
Gnomad4 EAS
AF:
0.241
Gnomad4 SAS
AF:
0.167
Gnomad4 FIN
AF:
0.0352
Gnomad4 NFE
AF:
0.0708
Gnomad4 OTH
AF:
0.111
Alfa
AF:
0.0871
Hom.:
408
Bravo
AF:
0.112
Asia WGS
AF:
0.172
AC:
599
AN:
3478
EpiCase
AF:
0.0776
EpiControl
AF:
0.0820

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: reviewed by expert panel
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Glanzmann thrombasthenia Benign:2
Benign, reviewed by expert panelcurationClinGen Platelet Disorders Variant Curation Expert Panel, ClinGenDec 01, 2022After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.882T>C (p.Pro294=), no individuals with Glanzmann thrombasthenia were reported with the variant. Moreover, the variant has a minor allele frequency of 0.2463 (4912/19940 alleles) in gnomAD, found in the East Asian population, which is considerably higher than the expected frequency of the disease (BA1). In Silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing at a nucleotide site that is not highly conserved. In conclusion the criteria BA1, BP4, and BP7 were applied to reach a classification of benign. -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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. -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
12
DANN
Benign
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

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: rs5919; hg19: chr17-45364540; COSMIC: COSV71383340; COSMIC: COSV71383340; API