rs2190503

Positions:

• chr7-50674920-A-G
• chr7-50674920-A-T

Variant summary

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

The NM_001350814.2(GRB10):​c.140-262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,150 control chromosomes in the GnomAD database, including 57,912 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 0.87 (57912 hom., cov: 31)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRB10	NM_001350814.2	c.140-262T>C		intron_variant		ENST00000401949.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRB10	ENST00000401949.6	c.140-262T>C		intron_variant		1	NM_001350814.2	P3

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132578 AN: 152032 Hom.: 57882 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.864

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.872 AC: 132666 AN: 152150 Hom.: 57912 Cov.: 31 AF XY: 0.871 AC XY: 64750 AN XY: 74366

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.920

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.886

Alfa AF: 0.875 Hom.: 77264

Bravo AF: 0.878

Asia WGS AF: 0.902 AC: 3138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2190503; hg19: chr7-50742617;