Variant chr7-50604057-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

Clinical Significance

Benign criteria provided, single submitter 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]

GRB10 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

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_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.326 with no splicing effect.

BS2

High AC in GnomAd4 at 1139 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRB10	NM_001350814.2 linkuse as main transcript	c.1485C>T	p.His495=	synonymous_variant	17/19	ENST00000401949.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRB10	ENST00000401949.6 linkuse as main transcript	c.1485C>T	p.His495=	synonymous_variant	17/19	1	NM_001350814.2	P3	Q13322-1

Frequencies

GnomAD3 genomes

AF:

0.00748

AC:

1139

AN:

152210

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00748

AC:

1139

AN:

152328

Hom.:

Cov.:

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.:

Bravo

AF:

0.00751

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0131

EpiControl

AF:

0.0118

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

GRB10: BP4, BP7, BS1, BS2 -

GRB10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over