7-50717751-C-T

Variant names:

• chr7-50717751-C-T
• rs1978208
• NM_001350814.2:c.52-13843G>A

Variant summary

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

The NM_001350814.2(GRB10):​c.52-13843G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,154 control chromosomes in the GnomAD database, including 41,783 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 (41783 hom., cov: 33)
• Consequence: GRB10 NM_001350814.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRB10	NM_001350814.2	c.52-13843G>A		intron_variant	Intron 4 of 18	ENST00000401949.6	NP_001337743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRB10	ENST00000401949.6	c.52-13843G>A		intron_variant	Intron 4 of 18	1	NM_001350814.2	ENSP00000385770.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109800 AN: 152036 Hom.: 41776 Cov.: 33

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.722 AC: 109835 AN: 152154 Hom.: 41783 Cov.: 33 AF XY: 0.725 AC XY: 53905 AN XY: 74388

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.852

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.834

Gnomad4 OTH AF: 0.759

Alfa AF: 0.806 Hom.: 25021

Bravo AF: 0.707

Asia WGS AF: 0.798 AC: 2774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.81

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: rs1978208; hg19: chr7-50785448;