NM_001350814.2:c.-46-7968A>G

Variant names:

• chr7-50740336-T-C
• rs12536500
• NM_001350814.2:c.-46-7968A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350814.2(GRB10):​c.-46-7968A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,110 control chromosomes in the GnomAD database, including 33,752 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 0.64 (33752 hom., cov: 32)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628
• Publications: 16 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.-46-7968A>G		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.-46-7968A>G		intron_variant	Intron 3 of 18	1	NM_001350814.2	ENSP00000385770.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96787 AN: 151992 Hom.: 33747 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.636 AC: 96815 AN: 152110 Hom.: 33752 Cov.: 32 AF XY: 0.640 AC XY: 47591 AN XY: 74362

African (AFR) AF: 0.328 AC: 13579 AN: 41454

American (AMR) AF: 0.731 AC: 11182 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2802 AN: 3472

East Asian (EAS) AF: 0.746 AC: 3857 AN: 5168

South Asian (SAS) AF: 0.763 AC: 3683 AN: 4824

European-Finnish (FIN) AF: 0.722 AC: 7638 AN: 10584

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51682 AN: 68000

Other (OTH) AF: 0.688 AC: 1452 AN: 2112

Alfa AF: 0.733 Hom.: 26164

Bravo AF: 0.623

Asia WGS AF: 0.737 AC: 2566 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	4.2
DANN	Benign	0.71
PhyloP100		0.63
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: rs12536500; hg19: chr7-50808033;