Variant 7-50674483-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001350814.2(GRB10):c.315G>A(p.Pro105Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,608,166 control chromosomes in the GnomAD database, including 235,632 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 24571 hom., cov: 34)

Exomes 𝑓: 0.54 ( 211061 hom. )

Consequence

GRB10
NM_001350814.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.40

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP7

Synonymous conserved (PhyloP=-3.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB10	NM_001350814.2 linkuse as main transcript	c.315G>A	p.Pro105Pro	synonymous_variant	6/19	ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6 linkuse as main transcript	c.315G>A	p.Pro105Pro	synonymous_variant	6/19	1	NM_001350814.2	ENSP00000385770.1		Q13322-1

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85492

AN:

152076

Hom.:

24547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.657

Gnomad AMI

AF:

0.574

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.545

Gnomad NFE

AF:

0.546

Gnomad OTH

AF:

0.582

GnomAD3 exomes

AF:

0.517

AC:

126579

AN:

244630

Hom.:

33360

AF XY:

0.513

AC XY:

68432

AN XY:

133322

show subpopulations

Gnomad AFR exome

AF:

0.666

Gnomad AMR exome

AF:

0.501

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.420

Gnomad SAS exome

AF:

0.461

Gnomad FIN exome

AF:

0.407

Gnomad NFE exome

AF:

0.548

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.535

AC:

779672

AN:

1455970

Hom.:

211061

Cov.:

AF XY:

0.533

AC XY:

385942

AN XY:

724574

show subpopulations

Gnomad4 AFR exome

AF:

0.651

Gnomad4 AMR exome

AF:

0.507

Gnomad4 ASJ exome

AF:

0.525

Gnomad4 EAS exome

AF:

0.363

Gnomad4 SAS exome

AF:

0.461

Gnomad4 FIN exome

AF:

0.414

Gnomad4 NFE exome

AF:

0.551

Gnomad4 OTH exome

AF:

0.536

GnomAD4 genome

AF:

0.562

AC:

85560

AN:

152196

Hom.:

24571

Cov.:

AF XY:

0.552

AC XY:

41038

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.657

Gnomad4 AMR

AF:

0.584

Gnomad4 ASJ

AF:

0.516

Gnomad4 EAS

AF:

0.397

Gnomad4 SAS

AF:

0.461

Gnomad4 FIN

AF:

0.399

Gnomad4 NFE

AF:

0.546

Gnomad4 OTH

AF:

0.582

Alfa

AF:

0.550

Hom.:

28320

Bravo

AF:

0.576

Asia WGS

AF:

0.518

AC:

1802

AN:

3478

EpiCase

AF:

0.544

EpiControl

AF:

0.549

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.2

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over