chr7-50779949-G-A

Position:

• chr7-50779949-G-A

Variant summary

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

The ENST00000401949.6(GRB10):​c.-217+678C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,988 control chromosomes in the GnomAD database, including 30,542 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 0.62 (30542 hom., cov: 32)
• Consequence: GRB10 ENST00000401949.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.-217+678C>T		intron_variant		ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6	c.-217+678C>T		intron_variant		1	NM_001350814.2	ENSP00000385770	P3

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93492 AN: 151868 Hom.: 30542 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.615 AC: 93505 AN: 151988 Hom.: 30542 Cov.: 32 AF XY: 0.607 AC XY: 45074 AN XY: 74264

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.676

Alfa AF: 0.710 Hom.: 21778

Bravo AF: 0.603

Asia WGS AF: 0.714 AC: 2485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1014384; hg19: chr7-50847646;