rs1024531

Positions:

• chr7-50746259-G-A
• chr7-50746259-G-C

Variant summary

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

The NM_001350814.2(GRB10):​c.-47+9628C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,964 control chromosomes in the GnomAD database, including 28,543 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 0.58 (28543 hom., cov: 33)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRB10	NM_001350814.2	c.-47+9628C>T		intron_variant		ENST00000401949.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRB10	ENST00000401949.6	c.-47+9628C>T		intron_variant		1	NM_001350814.2	P3

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88551 AN: 151846 Hom.: 28541 Cov.: 33

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.583 AC: 88559 AN: 151964 Hom.: 28543 Cov.: 33 AF XY: 0.574 AC XY: 42652 AN XY: 74264

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.743

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.650

Alfa AF: 0.639 Hom.: 4078

Bravo AF: 0.574

Asia WGS AF: 0.716 AC: 2491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1024531; hg19: chr7-50813956;