7-50628397-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350814.2(GRB10):c.505-1419G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,028 control chromosomes in the GnomAD database, including 48,097 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 0.79 (48097 hom., cov: 31)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRB10	NM_001350814.2	c.505-1419G>A		intron_variant		ENST00000401949.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRB10	ENST00000401949.6	c.505-1419G>A		intron_variant		1	NM_001350814.2	P3

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120621 AN: 151910 Hom.: 48062 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.811

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.794 AC: 120710 AN: 152028 Hom.: 48097 Cov.: 31 AF XY: 0.792 AC XY: 58818 AN XY: 74304

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.865

Gnomad4 ASJ AF: 0.749

Gnomad4 EAS AF: 0.932

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.811

Alfa AF: 0.789 Hom.: 55237

Bravo AF: 0.810

Asia WGS AF: 0.816 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.16
Dann	Benign	0.40

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

Other links and lift over

dbSNP: rs980716; hg19: chr7-50696094;