7-50658447-C-T

Variant names:

• chr7-50658447-C-T
• rs2237457
• NM_001350814.2:c.504+11275G>A

Variant summary

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

The NM_001350814.2(GRB10):​c.504+11275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,104 control chromosomes in the GnomAD database, including 6,679 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 (6679 hom., cov: 32)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.97
• Publications: 22 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.504+11275G>A		intron_variant	Intron 7 of 18	ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6	c.504+11275G>A		intron_variant	Intron 7 of 18	1	NM_001350814.2	ENSP00000385770.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40742 AN: 151986 Hom.: 6679 Cov.: 32

Gnomad AFR AF: 0.0799

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.268 AC: 40732 AN: 152104 Hom.: 6679 Cov.: 32 AF XY: 0.265 AC XY: 19711 AN XY: 74332

African (AFR) AF: 0.0797 AC: 3309 AN: 41506

American (AMR) AF: 0.341 AC: 5219 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1595 AN: 3472

East Asian (EAS) AF: 0.493 AC: 2549 AN: 5168

South Asian (SAS) AF: 0.272 AC: 1311 AN: 4820

European-Finnish (FIN) AF: 0.241 AC: 2543 AN: 10536

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23051 AN: 67992

Other (OTH) AF: 0.329 AC: 696 AN: 2116

Alfa AF: 0.313 Hom.: 6469

Bravo AF: 0.271

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.014
DANN	Benign	0.58
PhyloP100		-4.0
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: rs2237457; hg19: chr7-50726144;