Variant 7-50593090-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

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 (no stars).

Frequency

Genomes: 𝑓 0.082 ( 789 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8759 hom. )

Consequence

GRB10
NM_001350814.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.798

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 -14 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 no_assertion_criteria_provided, 0 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 linkuse as main transcript	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 linkuse as main transcript	c.1647C>T	p.Asp549=	synonymous_variant	19/19	1	NM_001350814.2	P3	Q13322-1

Frequencies

GnomAD3 genomes

AF:

0.0824

AC:

12530

AN:

152080

Hom.:

784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0808

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.0721

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0960

Gnomad OTH

AF:

0.0707

GnomAD3 exomes

AF:

0.105

AC:

26225

AN:

248592

Hom.:

1836

AF XY:

0.107

AC XY:

14434

AN XY:

134932

show subpopulations

Gnomad AFR exome

AF:

0.0164

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.0484

Gnomad EAS exome

AF:

0.0769

Gnomad SAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.0953

Gnomad OTH exome

AF:

0.0939

GnomAD4 exome

AF:

0.102

AC:

149541

AN:

1461778

Hom.:

8759

Cov.:

AF XY:

0.103

AC XY:

74953

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0147

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.0472

Gnomad4 EAS exome

AF:

0.0755

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.231

Gnomad4 NFE exome

AF:

0.0994

Gnomad4 OTH exome

AF:

0.0926

GnomAD4 genome

AF:

0.0824

AC:

12538

AN:

152198

Hom.:

789

Cov.:

AF XY:

0.0916

AC XY:

6813

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0181

Gnomad4 AMR

AF:

0.0814

Gnomad4 ASJ

AF:

0.0504

Gnomad4 EAS

AF:

0.0724

Gnomad4 SAS

AF:

0.137

Gnomad4 FIN

AF:

0.246

Gnomad4 NFE

AF:

0.0960

Gnomad4 OTH

AF:

0.0695

Alfa

AF:

0.0857

Hom.:

780

Bravo

AF:

0.0682

Asia WGS

AF:

0.0800

AC:

277

AN:

3478

EpiCase

AF:

0.0859

EpiControl

AF:

0.0850

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GRB10-related disorder

Benign:1

Benign, no assertion criteria provided

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.21

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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