7-50746259-G-A

Variant names:

• chr7-50746259-G-A
• rs1024531
• NM_001350814.2:c.-47+9628C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.-47+9628C>T		intron_variant	Intron 3 of 18	ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6	c.-47+9628C>T		intron_variant	Intron 3 of 18	1	NM_001350814.2	ENSP00000385770.1

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

African (AFR) AF: 0.307 AC: 12724 AN: 41444

American (AMR) AF: 0.587 AC: 8970 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2673 AN: 3466

East Asian (EAS) AF: 0.743 AC: 3848 AN: 5178

South Asian (SAS) AF: 0.670 AC: 3221 AN: 4810

European-Finnish (FIN) AF: 0.509 AC: 5362 AN: 10526

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49432 AN: 67946

Other (OTH) AF: 0.650 AC: 1372 AN: 2112

Alfa AF: 0.626 Hom.: 4112

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
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1024531; hg19: chr7-50813956;