7-50683393-T-C

Variant names:

• chr7-50683393-T-C
• rs10248619
• NM_001350814.2:c.140-8735A>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.140-8735A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 152,128 control chromosomes in the GnomAD database, including 40,598 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 0.72 (40598 hom., cov: 32)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 29 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.140-8735A>G		intron_variant	Intron 5 of 18	ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6	c.140-8735A>G		intron_variant	Intron 5 of 18	1	NM_001350814.2	ENSP00000385770.1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109626 AN: 152010 Hom.: 40594 Cov.: 32

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.721 AC: 109663 AN: 152128 Hom.: 40598 Cov.: 32 AF XY: 0.714 AC XY: 53123 AN XY: 74368

African (AFR) AF: 0.566 AC: 23462 AN: 41442

American (AMR) AF: 0.817 AC: 12500 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3041 AN: 3472

East Asian (EAS) AF: 0.907 AC: 4694 AN: 5178

South Asian (SAS) AF: 0.723 AC: 3487 AN: 4824

European-Finnish (FIN) AF: 0.603 AC: 6379 AN: 10578

Middle Eastern (MID) AF: 0.880 AC: 257 AN: 292

European-Non Finnish (NFE) AF: 0.786 AC: 53449 AN: 68018

Other (OTH) AF: 0.784 AC: 1654 AN: 2110

Alfa AF: 0.778 Hom.: 164833

Bravo AF: 0.730

Asia WGS AF: 0.812 AC: 2823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.76
DANN	Benign	0.42
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10248619; hg19: chr7-50751090;