7-50789095-G-A

Position:

• chr7-50789095-G-A

Variant summary

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

The ENST00000335866.7(GRB10):​c.-294+4129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,134 control chromosomes in the GnomAD database, including 37,907 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 0.68 (37907 hom., cov: 33)
• Consequence: GRB10 ENST00000335866.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB10	NM_001001555.3	c.-294+4129C>T		intron_variant			NP_001001555.1
GRB10	NM_001350815.2	c.83+3347C>T		intron_variant			NP_001337744.1
GRB10	NM_001350816.3	c.-410+3347C>T		intron_variant			NP_001337745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000335866.7	c.-294+4129C>T		intron_variant		1		ENSP00000338543	A1
GRB10	ENST00000402497.6	c.-124+4129C>T		intron_variant		5		ENSP00000385748	A1
GRB10	ENST00000439044.7	c.-520+4129C>T		intron_variant		5		ENSP00000413023

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103305 AN: 152016 Hom.: 37915 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.679 AC: 103309 AN: 152134 Hom.: 37907 Cov.: 33 AF XY: 0.673 AC XY: 50028 AN XY: 74384

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.878

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.722

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.822

Gnomad4 OTH AF: 0.744

Alfa AF: 0.801 Hom.: 64965

Bravo AF: 0.669

Asia WGS AF: 0.801 AC: 2785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7791286; hg19: chr7-50856792;