chr7-50686982-G-A

Variant names:

• chr7-50686982-G-A
• rs2282930
• NM_001350814.2:c.140-12324C>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.140-12324C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,062 control chromosomes in the GnomAD database, including 5,762 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 0.27 (5762 hom., cov: 32)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710
• Publications: 12 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.140-12324C>T		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.140-12324C>T		intron_variant	Intron 5 of 18	1	NM_001350814.2	ENSP00000385770.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40510 AN: 151944 Hom.: 5754 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.267 AC: 40544 AN: 152062 Hom.: 5762 Cov.: 32 AF XY: 0.264 AC XY: 19626 AN XY: 74346

African (AFR) AF: 0.300 AC: 12422 AN: 41420

American (AMR) AF: 0.272 AC: 4163 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1222 AN: 3472

East Asian (EAS) AF: 0.507 AC: 2621 AN: 5172

South Asian (SAS) AF: 0.238 AC: 1147 AN: 4818

European-Finnish (FIN) AF: 0.194 AC: 2052 AN: 10574

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16019 AN: 67996

Other (OTH) AF: 0.278 AC: 589 AN: 2116

Alfa AF: 0.253 Hom.: 15597

Bravo AF: 0.280

Asia WGS AF: 0.295 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.47
DANN	Benign	0.75
PhyloP100		-0.71
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: rs2282930; hg19: chr7-50754679;