chr7-50593090-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_001350814.2(GRB10):c.1647C>T(p.Asp549=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,613,976 control chromosomes in the GnomAD database, including 9,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.082 ( 789 hom., cov: 32)
Exomes 𝑓: 0.10 ( 8759 hom. )
Consequence
GRB10
NM_001350814.2 synonymous
NM_001350814.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.798
Genes affected
GRB10 (HGNC:4564): (growth factor receptor bound protein 10) The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor receptors. Overexpression of some isoforms of the encoded protein inhibits tyrosine kinase activity and results in growth suppression. This gene is imprinted in a highly isoform- and tissue-specific manner, with expression observed from the paternal allele in the brain, and from the maternal allele in the placental trophoblasts. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 7-50593090-G-A is Benign according to our data. Variant chr7-50593090-G-A is described in ClinVar as [Benign]. Clinvar id is 3060352.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.798 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRB10 | NM_001350814.2 | c.1647C>T | p.Asp549= | synonymous_variant | 19/19 | ENST00000401949.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRB10 | ENST00000401949.6 | c.1647C>T | p.Asp549= | synonymous_variant | 19/19 | 1 | NM_001350814.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0824 AC: 12530AN: 152080Hom.: 784 Cov.: 32
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GnomAD3 exomes AF: 0.105 AC: 26225AN: 248592Hom.: 1836 AF XY: 0.107 AC XY: 14434AN XY: 134932
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GnomAD4 exome AF: 0.102 AC: 149541AN: 1461778Hom.: 8759 Cov.: 32 AF XY: 0.103 AC XY: 74953AN XY: 727200
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GnomAD4 genome ? AF: 0.0824 AC: 12538AN: 152198Hom.: 789 Cov.: 32 AF XY: 0.0916 AC XY: 6813AN XY: 74382
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
GRB10-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 22, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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RBP_binding_hub_radar
RBP_regulation_power_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at