7-50597225-A-G

Position:

• chr7-50597225-A-G

Variant summary

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

The NM_001350814.2(GRB10):​c.1545-1695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,178 control chromosomes in the GnomAD database, including 9,259 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 0.33 (9259 hom., cov: 33)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRB10	NM_001350814.2	c.1545-1695T>C		intron_variant		ENST00000401949.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRB10	ENST00000401949.6	c.1545-1695T>C		intron_variant		1	NM_001350814.2	P3

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50488 AN: 152060 Hom.: 9255 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.332 AC: 50495 AN: 152178 Hom.: 9259 Cov.: 33 AF XY: 0.327 AC XY: 24364 AN XY: 74396

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.365

Alfa AF: 0.391 Hom.: 18445

Bravo AF: 0.332

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.4
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs12540874; hg19: chr7-50664922;