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7-50604057-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001350814.2(GRB10):c.1485C>T(p.His495=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00931 in 1,613,962 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0075 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0095 ( 92 hom. )

Consequence

GRB10
NM_001350814.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.326
Variant links:
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 -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-50604057-G-A is Benign according to our data. Variant chr7-50604057-G-A is described in ClinVar as [Benign]. Clinvar id is 2657500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.326 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1139 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRB10NM_001350814.2 linkuse as main transcriptc.1485C>T p.His495= synonymous_variant 17/19 ENST00000401949.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRB10ENST00000401949.6 linkuse as main transcriptc.1485C>T p.His495= synonymous_variant 17/191 NM_001350814.2 P3Q13322-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00748
AC:
1139
AN:
152210
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00198
Gnomad AMI
AF:
0.00439
Gnomad AMR
AF:
0.00680
Gnomad ASJ
AF:
0.0158
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.0141
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0105
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.00815
AC:
2034
AN:
249582
Hom.:
22
AF XY:
0.00808
AC XY:
1094
AN XY:
135410
show subpopulations
Gnomad AFR exome
AF:
0.00174
Gnomad AMR exome
AF:
0.00550
Gnomad ASJ exome
AF:
0.0158
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00255
Gnomad FIN exome
AF:
0.0139
Gnomad NFE exome
AF:
0.0108
Gnomad OTH exome
AF:
0.00891
GnomAD4 exome
AF:
0.00950
AC:
13883
AN:
1461634
Hom.:
92
Cov.:
31
AF XY:
0.00930
AC XY:
6761
AN XY:
727154
show subpopulations
Gnomad4 AFR exome
AF:
0.00176
Gnomad4 AMR exome
AF:
0.00561
Gnomad4 ASJ exome
AF:
0.0147
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00307
Gnomad4 FIN exome
AF:
0.0130
Gnomad4 NFE exome
AF:
0.0104
Gnomad4 OTH exome
AF:
0.00873
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00748
AC:
1139
AN:
152328
Hom.:
5
Cov.:
33
AF XY:
0.00760
AC XY:
566
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.00197
Gnomad4 AMR
AF:
0.00680
Gnomad4 ASJ
AF:
0.0158
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.0141
Gnomad4 NFE
AF:
0.0105
Gnomad4 OTH
AF:
0.00805
Alfa
AF:
0.00960
Hom.:
7
Bravo
AF:
0.00751
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0131
EpiControl
AF:
0.0118

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2023GRB10: BP4, BP7, BS1, BS2 -
GRB10-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 01, 2019This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
7.8
Dann
Benign
0.61
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs61756585; hg19: chr7-50671754; COSMIC: COSV60010655; COSMIC: COSV60010655; API