chr7-50604017-G-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001350814.2(GRB10):c.1525C>G(p.Gln509Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000558 in 1,613,636 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00042 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00057 ( 3 hom. )
Consequence
GRB10
NM_001350814.2 missense
NM_001350814.2 missense
Scores
1
9
7
Clinical Significance
Conservation
PhyloP100: 9.79
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.024909943).
BP6
?
Variant 7-50604017-G-C is Benign according to our data. Variant chr7-50604017-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3043075.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 64 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRB10 | NM_001350814.2 | c.1525C>G | p.Gln509Glu | missense_variant | 17/19 | ENST00000401949.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRB10 | ENST00000401949.6 | c.1525C>G | p.Gln509Glu | missense_variant | 17/19 | 1 | NM_001350814.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000420 AC: 64AN: 152234Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000585 AC: 146AN: 249588Hom.: 0 AF XY: 0.000716 AC XY: 97AN XY: 135410
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GnomAD4 exome AF: 0.000572 AC: 836AN: 1461284Hom.: 3 Cov.: 31 AF XY: 0.000646 AC XY: 470AN XY: 727012
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GnomAD4 genome ? AF: 0.000420 AC: 64AN: 152352Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26AN XY: 74502
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
GRB10-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 06, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;.;.;D;.;D;.;.;.;.;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;.;.;N;N;N;N;.;N;.
REVEL
Uncertain
Sift
Benign
T;T;T;T;.;.;T;D;T;T;.;T;.
Sift4G
Benign
T;T;T;T;.;.;T;T;T;T;.;T;.
Polyphen
0.048, 0.34, 0.15
.;B;.;.;.;.;.;B;B;.;.;.;B
Vest4
MVP
MPC
1.5
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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