rs2074778

Positions:

• chr7-50626732-G-A
• chr7-50626732-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.661+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,438,716 control chromosomes in the GnomAD database, including 80,942 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 0.38 (12050 hom., cov: 33)
  • Exomes 𝑓: 0.32 (68892 hom.)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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 (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRB10	NM_001350814.2	c.661+90C>T		intron_variant		ENST00000401949.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRB10	ENST00000401949.6	c.661+90C>T		intron_variant		1	NM_001350814.2	P3

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58362 AN: 151994 Hom.: 12030 Cov.: 33

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.323 AC: 415804 AN: 1286604 Hom.: 68892 AF XY: 0.320 AC XY: 207680 AN XY: 648484

Gnomad4 AFR exome AF: 0.546

Gnomad4 AMR exome AF: 0.356

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.334

GnomAD4 genome AF: 0.384 AC: 58427 AN: 152112 Hom.: 12050 Cov.: 33 AF XY: 0.377 AC XY: 28055 AN XY: 74394

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.393

Alfa AF: 0.284 Hom.: 1551

Bravo AF: 0.404

Asia WGS AF: 0.398 AC: 1382 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	0.041
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2074778; hg19: chr7-50694429;